Optically active 2,5-bisaryl-Δ1-pyrrolines and their use as pest control agents

ABSTRACT

Novel optically active Δ 1 -pyrrolines of the formula (I) 
                         
in which
     R 1 , R 2 , R 3 , R 4 , and m are each as defined in the description,   a plurality of the processes for preparing these substances and their use for controlling pests.

The present patent application has been filed under 35 U.S.C. 371 as anational stage application of PCT/EP01/10424, filed Sep. 10, 2001, whichwas published in German as International Patent Publication WO 02/24643on Mar. 28, 2002, and is entitled to the right of priority of GermanPatent Application 100 47 110.2, filed Sep. 22, 2000.

The invention relates to novel optically active2,5-bisaryl-Δ¹-pyrrolines, processes for their preparation and to theiruse as pesticides.

Racemic Δ¹-pyrroline pesticides have already been described inWO00/21958, WO 99/59968, WO 99/59967 and WO 98/22438.

However, the efficacy and/or duration of action of these prior-artracemates is, in particular against certain organisms and/or at lowapplication rates, not entirely satisfactory in all areas of use.

Owing to the multifarious requirements that modem pesticides have tomeet, for example with respect to efficacy, duration of action, activityspectrum, use spectrum, toxicity, combination with other activecompounds, combination with formulation auxiliaries or synthesis, andowing to the possible occurrence of resistance, however, the developmentof such substances can never be considered as being concluded, and thereis always a great need for novel compounds which, at least in someaspects, offer advantages over the known compounds.

It is an object of the present invention to provide optically activecompounds of the general formula (I). When used as pesticides, thesecompounds allow the application rates to be reduced.

The present invention provides novel optically active Δ¹-pyrrolines ofthe formula (I)

in which

-   * represents a chiral carbon atom having the (R)-configuration,-   m represents 0, 1, 2, 3 or 4,-   R¹ represents halogen or methyl,-   R² represents hydrogen or halogen,-   R³ represents hydrogen, halogen, hydroxyl, alkyl, alkenyl, alkinyl,    halogenoalkyl, halogenoalkenyl, alkoxy, —S(O)_(o)R⁶, —OSO₂R⁶,    bisalkoxyborane, —B(OH)₂ or represents phenyl which is optionally    mono- or polysubstituted by radicals from the list W¹,-   R⁴ represents halogen, alkyl, alkoxy, halogenoalkyl, halogenoalkoxy    or —S(O)_(o)R⁶,-   W¹ represents cyano, halogen, hydroxyl, alkyl, alkoxy,    halogenoalkyl, halogenoalkoxy, alkenyl, halogenoalkenyl, alkenyloxy,    halogenoalkenyloxy, alkoxycarbonyl, trialkylsilyl, trialkylsilyloxy,    —CONH₂, —NR⁷R⁸, —S(O)_(o)R⁶ or —SO₂NR⁷R⁸,-   o represents 0, 1 or 2,-   R⁶ represents hydrogen, alkyl or halogenoalkyl,-   R⁷ and R⁸ independently of one another each represent hydrogen,    alkyl, halogenoalkyl or together represent alkylene or    alkoxyalkylene.

In the formulae of all the compounds described above and below, anasterisk (*) denotes in each case a chiral carbon atom with(R)-configuration.

Moreover, it has been found that optically active compounds of theformula (I) are obtained when

-   A) racemic compounds of the formula (I-rac)

-   -   in which    -   R¹, R², R³, R⁴ and m are each as defined above,    -   are chromatographed on a stationary chiral silica gel phase in        the presence of an eluent or an eluent mixture as liquid phase,        or

-   B) (i) compounds of the formula (I-a)

-   -   in which    -   R¹, R², R⁴ and m are each as defined above and    -   X¹ represents Cl, Br, I, —OSO₂CF₃, —OSO₂(CF₂)₃CF₃,    -   are reacted with organometallic compounds of the formula (II)        A-M  (II)    -    in which    -   A represents phenyl which is optionally mono- or polysubstituted        by radicals from the list W¹,    -   where W¹ is as defined above and    -   M represents —B(OH)₂, Sn(^(n)Bu)₃ or ZnCl,    -   M furthermore represents MgCl,    -   in the presence of a catalyst, if appropriate in the presence of        an acid binder and if appropriate in the presence of a diluent,        or

-   (ii) compounds of the formula (I-b)

-   -   in which    -   R¹, R², R⁴ and m are each as defined above,    -   X² represents —B(OH)₂,        (4,4,5,5-tetramethyl-1,3,2-dioxoborolan)-2-yl,        (5,5-dimethyl-1,3,2-dioxoborinan)-2-yl,        (4,4,6-trimethyl-1,3,2-dioxoborinan)-2-yl,        1,3,2-benzodioxaborol-2-yl, Sn(^(n)Bu)₃ or ZnCl,    -   are reacted with aromatic compounds of the formula (III)        T-A  (III)    -    in which    -   A represents phenyl which is optionally mono- or polysubstituted        by radicals from the list W¹,    -   where W¹ is as defined above, and    -   T represents Cl, Br, I, —OSO₂CF₃, —OSO₂(CF₂)₃CF₃,    -   in the presence of a catalyst, if appropriate in the presence of        an acid binder and if appropriate in the presence of a diluent,        or

-   (iii) compounds of the formula (I-a)

-   -   in which    -   R¹, R², R⁴, X¹ and m are each as defined above,    -   are reacted in a tandem reaction with aromatic compounds of the        formula (III)        T-A  (III)    -    in which    -   A and T are each as defined above,    -   in the presence of a catalyst, in the presence of        4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bis-1,3,2-dioxaborolane or        of 5,5,5′,5′-tetramethyl-2,2′-bis-1,3,2-dioxaborinane or of        4,4,4′,4′,6,6′-hexamethyl-2,2′-bis-1,3,2-dioxaborinane or of        2,2′-bis-1,3,2-benzodioxaborole and, if appropriate, in the        presence of an acid binder and, if appropriate, in the presence        of a diluent, or

-   C) optically active aminoketones of the formula (IV)

-   -   in which    -   R¹, R², R³, R⁴ and m are each as defined above,    -   are deprotected by treatment with a Lewis acid or protic acid        and the amine that is formed in situ is cyclized in the presence        of an acid.

Finally, it has been found that the compounds of the formula (I)according to the invention have very good insecticidal properties andcan be used both in crop protection and in the protection of materialsfor controlling undesirable pests such as insects.

Surprisingly, the compounds of the formula (I) according to theinvention have considerably better insecticidal activity than the knownracemates, which are likewise known to be highly active compounds havinginsecticidal properties, and than the (S)-configured analogues.

Surprisingly, the column material for separating the racemic compoundsof the formula (I-rac) used in process (A), which was selected from alarge number of commercially available solid phases tested, is the onlymaterial that affords the corresponding enantiomers in high purity andwith high yield.

The formula (I) provides a general definition of the compounds accordingto the invention. Preferred substituents or ranges of the radicalslisted under the formulae mentioned above and below are illustratedbelow.

-   m preferably represents 0, 1, 2 or 3.-   R¹ preferably represents fluorine, chlorine, bromine or methyl.-   R² preferably represents hydrogen, fluorine, chlorine or bromine.-   R³ preferably represents hydrogen, fluorine, chlorine, bromine,    iodine, hydroxyl, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkinyl,    C₁-C₆-halogenoalkyl, C₂-C₆-halogenoalkenyl, C₁-C₆-alkoxy,    —S(O)_(o)R⁶, —OSO₂R⁶, bis(C₄-C₈-alkoxy)borane, —B(OH)₂ or represents    phenyl which is optionally mono- or polysubstituted by radicals from    the list W¹.-   R⁴ preferably represents halogen, C₁-C₆-alkyl, C₁-C₆-alkoxy,    C₁-C₆-halogenoalkyl, C₁-C₆-halogenoalkoxy or —S(O)_(o)R⁶.-   W¹ preferably represents cyano, halogen, hydroxyl, C₁-C₆-alkyl,    C₁-C₆-alkoxy, C₁-C₆-halogenoalkyl, C₁-C₆-halogenoalkoxy,    C₂-C₆-halogenoalkenyloxy, C₁-C₆-alkoxycarbonyl,    tri(C₁-C₄-alkyl)silyl, tri(C₁-C₄-alkyl)silyloxy, —S(O)_(o)R⁶ or    —SO₂NR⁷R⁸.-   o preferably represents 0, 1 or 2.-   R⁶ preferably represents hydrogen, C₁-C₆-alkyl or    C₁-C₆-halogenoalkyl.-   R⁷ and R⁸ independently of one another each preferably represent    hydrogen, C₁-C₆-alkyl, C₁-C₆-halogenoalkyl or together represent    C₂-C₆-alkylene or C₁-C₄-alkoxy-C₁-C₄-alkylene (for example    morpholine).-   m particularly preferably represents 0, 1, or 2.-   R¹ particularly preferably represents fluorine, chlorine or methyl.-   R² particularly preferably represents hydrogen, fluorine or    chlorine.-   R³ particularly preferably represents hydrogen, fluorine, chlorine,    bromine, hydroxyl, C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkinyl,    C₁-C₆-alkoxy; represents in each case fluorine- or    chlorine-substituted C₁-C₆-alkyl or C₂-C₆-alkenyl; represents    —S(O)_(o)R⁶, —OSO₂R⁶, (5,5-dimethyl-1,3,2-dioxoborinan)-2-yl,    (4,4,5,5-tetramethyl-1,3,2-dioxoborolan)-2-yl,    (4,4,6-trimethyl-1,3,2-dioxoborinan)-2-yl,    1,3,2-benzodioxaborol-2-yl, —B(OH)₂ or represents phenyl which is    optionally mono- to trisubstituted by radicals from the list W¹.-   R⁴ particularly preferably represents fluorine, chlorine, bromine,    C₁-C₆-alkyl, C₁-C₆-alkoxy,in each case fluorine- or    chlorine-substituted C₁-C₆-alkyl or C₁-C₆-alkoxy or represents    —S(O)_(o)R⁶. p0 W¹ particularly preferably represents cyano,    fluorine, chlorine, bromine, iodine, hydroxyl, C₁-C₄-alkyl,    C₁-C₄-alkoxy, in each case fluorine- or chlorine-substituted    C₁-C₄-alkyl, C₁-C₄-alkoxy, C₂-C₆-alkenyloxy, represents    C₁-C₄-alkoxycarbonyl, —OSi(Me₂)t-Bu, —S(O)_(o)R⁶ or —SO₂NR⁷R⁸.-   o particularly preferably represents 0, 1, or 2.-   R⁶ particularly preferably represents hydrogen, C₁-C₆-alkyl or    represents fluorine- or chlorine-substituted C₁-C₄-alkyl.-   R⁷ and R⁸ independently of one another each particularly preferably    represent hydrogen, C₁-C₆-alkyl, fluorine- or chlorine-substituted    C₁-C₆-alkyl, or together represent C₄-C₅-alkylene.-   m very particularly preferably represents 0, 1 or 2.-   R¹ very particularly preferably represents fluorine, chlorine or    methyl.-   R² very particularly preferably represents hydrogen, fluorine or    chlorine.-   R³ very particularly preferably represents hydrogen, chlorine,    bromine, hydroxyl, methyl, ethyl, n-propyl, isopropyl, n-butyl,    isobutyl, sec-butyl, tert-butyl, 2-propenyl, butenyl, propargyl,    butinyl, methoxy, ethoxy, n-propoxy, n-butoxy, isobutoxy,    sec-butoxy, tert-butoxy, —SO₂CF₃, —SO₂(CF₂)₃CF₃, —OSO₂CF₃,    —OSO₂(CF₂)₃CF₃, (5,5-dimethyl-1,3,2-dioxoborinan)-2-yl,    (4,4,5,5-tetramethyl-1,3,2-dioxoborolan)-2-yl,    (4,4,6-trimethyl-1,3,2-dioxoborinan)-2-yl,    1,3,2-benzodioxaborol-2-yl, —B(OH)₂ or represents fluorine- or    chlorine-substituted C₁-C₄-alkyl or represents phenyl which is    optionally mono- to trisubstituted by radicals from the list W¹.-   R³ furthermore very particularly preferably represents isopropoxy.-   R⁴ very particularly preferably represents fluorine, chlorine,    bromine, methyl, ethyl, methoxy, ethoxy, trifluoromethyl,    difluoromethoxy, trifluoromethoxy or —SO₂CF₃.-   W¹ furthermore very particularly preferably represents cyano,    fluorine, chlorine, bromine, hydroxyl, methyl, ethyl, n-propyl,    isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, methoxy,    ethoxy, n-propoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy,    trifluoromethoxy, difluoromethoxy, —CF₃, —CHF₂, —CClF₂, —CF₂CHFCl,    —CF₂CH₂F, —CF₂CCl₃, —CH₂CF₃, —CF₂CHFCF₃, —CH₂CF₂H, —CH₂CF₂CF₃,    —CF₂CF₂H, —CF₂CHFCF₃, —OCF₂CF₂H, —OCF═CF₂, —SCF₃, —SOCF₃, —SO₂CF₃,    —SCHF₂, —SOCHF₂, —SO₂CHF₂, —OSi(Me₂)t-Bu, —SO₂NMe₂ or —CO₂Et.-   W¹ furthermore very particularly preferably represents isopropoxy.

Preference is furthermore given to compounds of the formulae (I-c),(I-d), (I-e), (I-f) and (I-g)

in which in each case

-   R³ is as defined above and-   R⁴⁻¹ represents hydrogen, methoxy or ethoxy.

Preference is furthermore given to compounds of the formulae (I-h),(I-i), (I-j), (I-k) and (I-l)

in which in each case

-   W¹ is as defined above.

In the definitions mentioned above, oxyalkylene and thioalkylenerepresent —O-alkyl- and —S-alkyl-, respectively, and alkyleneoxy andalkylenethio represent -alkyl-O— and -alkyl-S—, respectively,oxyalkyleneoxy represents —O-alkyl-O—.

Preference, particular preference and very particular preference isgiven to compounds which carry the substituents mentioned above as beingpreferred, particularly preferred and very particularly preferred,respectively.

Saturated or unsaturated hydrocarbon radicals, such as alkyl or alkenyl,can in each case be straight-chain or branched as far as this ispossible, including in combination with heteroatoms, such as, forexample, in alkoxy.

Optionally substituted radicals can be mono- or polysubstituted, wherein the case of polysubstitution the substituents can be identical ordifferent. A plurality of radicals having the same indices, such as, forexample, m radicals R⁴ for m>1, can be identical or different.

However, the abovementioned general or preferred radical definitions orillustrations can also be combined with one another as desired, i.e.including combinations between the respective ranges and preferredranges. They apply to the end products and also, correspondingly, to theprecursors and intermediates.

Illustration of the Processes and Intermediates:

Process A

The formula (I-rac) provides a general definition of the racemiccompounds required as starting materials for carrying out the Process Aaccording to the invention. In this formula, R¹, R², R³, R⁴ and m eachpreferably, particularly preferably and very particularly preferablyhave those meanings which have already been mentioned in connection withthe description of the compounds of the formula (I) according to theinvention as being preferred, particularly preferred etc. for theseradicals.

The racemic compounds of the formula (I-rac) used for carrying out theProcess A according to the invention are known and can be prepared byknown processes (WO 00/21958, WO 99/59968, WO 99/59967 and WO 98/22438).

When carrying out the Process A according to the invention, methods ofpreparative chromatography, preferably the High Performance LiquidChromatography (HPLC) method, are employed. For this purpose, a chiralstationary silica gel phase is used. A silica gel modified bytris(3,5-dimethylphenylcarbamate)-cellulose has been found to beparticularly suitable for separating the compounds of the formula(I-rac) into the two enantiomers. This separation material iscommercially available. However, it is also possible to use otherstationary phases as chromatography material.

Process B

Using(2R)-5-(2,6-difluorophenyl)-2-(4-trifluoromethylsulphonyloxyphenyl)-3,4-dihydro-2H-pyrrole,4-trifluoromethoxyphenylboronic acid and a palladium catalyst asstarting materials, the Process B(i) according to the invention can beillustrated by the equation below.

Using(2R)-5-(2,6-difluorophenyl)-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-3,4-dihydro-2H-pyrrole,4-trifluoromethoxy-bromophenyl and a palladium catalyst, the ProcessB(ii) according to the invention can be illustated by the equationbelow.

Using(2R)-5-(2,6-difluorophenyl)-2-(4-bromo-phenyl)-3,4-dihydro-2H-pyrrole,4-trifluoromethoxy-bromophenyl, a palladium catalyst and4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bis-1,3,2-dioxaborolane as startingmaterials, the Process B(iii) according to the invention can beillustrated by the equation below.

The formulae (I-a) and (I-b) provide a general definition of thecompounds required as starting materials for carrying out the Process Baccording to the invention. In these formulae, R¹, R², R⁴ and m eachpreferably, particularly preferably and very particularly preferablyhave those meanings which have already been mentioned in connection withthe description of the compounds of the formula (I) according to theinvention as being preferred, particularly preferred etc. for theseradicals.

-   X¹ preferably represents Cl, Br, —OSO₂CF₃ or —OSO₂(CF₂)₃CF₃.-   X¹ particularly preferably represents Cl, Br or —OSO₂CF₃.-   X¹ very particularly preferably represents Cl, Br or —OSO₂CF₃.-   X² preferably represents —B(OH)₂,    (4,4,5,5-tetramethyl-1,3,2-dioxoborolan)-2-yl,    (5,5-dimethyl-1,3,2-dioxoborinan)-2-yl,    (4,4,6-trimethyl-1,3,2-dioxoborinan)-2-yl,    1,3,2-benzodioxaborol-2-yl, Sn(^(n)Bu)₃ or ZnCl.-   X² particularly preferably represents —B(OH)₂,    (4,4,5,5-tetramethyl-1,3,2-dioxoborolan)-2-yl,    (5,5-dimethyl-1,3,2-dioxoborinan)-2-yl,    (4,4,6-trimethyl-1,3,2-dioxoborinan)-2-yl or    1,3,2-benzodioxaborol-2-yl.-   X² very particularly preferably represents —B(OH)₂,    (4,4,5,5-tetramethyl-1,3,2-dioxoborolan)-2-yl or    (4,4,6-trimethyl-1,3,2-dioxoborinan)-2-yl.

Here, the radicals R⁶, R⁷ and R⁸ each preferably, particularlypreferably and very particularly preferably have those meanings whichhave already been mentioned in connection with the description of thecompounds of the formula (I) according to the invention as beingpreferred, particularly preferred etc. for these radicals.

Optically active cyclic imines of the formulae (I-a) and (I-b) are noveland are prepared analogously to Process A or C.

The formula (II) provides a general definition of the organometalliccompounds required as starting materials for carrying out the ProcessB(i) according to the invention.

-   A preferably represents phenyl which is unsubstituted or mono- to    tetrasubstituted by radicals from the list W¹.-   A particularly preferably represents phenyl which is unsubstituted    or mono- or disubstituted by radicals from the list W¹.-   A very particularly preferably represents phenyl which is mono- or    disubstituted by radicals from the list W¹.

Here, W¹ preferably, particularly preferably and very particularlypreferably has those meanings which have already been mentioned inconnection with the description of the compounds of the formula (I)according to the invention as being preferred, particularly preferredetc. for these radicals.

-   M preferably represents —B(OH)₂, Sn(^(n)Bu)₃ or ZnCl.-   M furthermore preferably represents MgCl.-   M particularly preferably represents —B(OH)₂ or Sn(^(n)Bu)₃.-   M very particularly preferably represents —B(OH)₂.

Some of the organometallic compounds of the formula (II) are known.However, boronic acids [for example in the case where M=—B(OH)₂], forexample, can also be prepared from (bromo)aromatics by lithiation orBr—Li (Mg) exchange and subsequent reaction with tris-alkoxyboroncompounds (cf., for example, Tetrahedron Lett. 1993, 34, 8237-8240).

The formula (III) provides a general definition of the aromaticsrequired as starting materials for carrying out the Processes B(ii) andB(iii) according to the invention. Here A preferably, particularlypreferably and very particularly preferably represents those radicalswhich have already been mentioned in the description of the compounds ofthe formula (II) as being preferred, particularly preferred and veryparticularly preferred, respectively.

-   T preferably represents Cl, Br, —OSO₂CF₃ or —OSO₂(CF₂)₃CF₃.-   T particularly preferably represents Cl, Br or —OSO₂CF₃.-   T very particularly preferably represents Br or —OSO₂CF₃.

Aromatics of the formula (III) are generally known and/or commerciallyavailable.

The Process B(iii) according to the invention can be carried out in twovariants. It is possible to initially charge either a compound of theformula (I-a) or a compound of the formula (III). Process B(iii) can beconsidered to be a tandem reaction of Processes B(i) and B(ii).

When carrying out the Process B according to the invention, a palladiumcatalyst is generally used which for its part can be used with orwithout addition of further ligands. The catalyst used is preferablyPdCl₂(dppf) [dppf=1,1′-bis(diphenylphosphino)ferrocene], Pd(PPh₃)₄,PdCl₂(PPh₃)₂, PdCl₂(CH₃CN)₂, Pd₂(dba)₃ [dba=dibenzylideneacetone] orPd(OAc)₂, particularly preferably PdCl₂(dppf), Pd(PPh₃)₄, PdCl₂(PPh₃)₂,or Pd(OAc)₂, very particularly preferably PdCl₂(dppf) or Pd(PPh₃)₄.

When carrying out the Process B(i) according to the invention, mostpreference is given to using PdCl₂(dppf), Pd(PPh₃)₄ or Pd(OAc)₂.

When carrying out the Process B(ii) according to the invention, mostpreference is given to using Pd₂(dba)₃.

When carrying out the Process B(iii) according to the invention, mostpreference is given to using PdCl₂(dppf) in the first step andPdCl₂(dppf), Pd(PPh₃)₄ or Pd(OAc)₂ in the second step of the tandemreaction.

Suitable ligands are triarylphosphines, trialkylphosphines or arsines.Preference is given to using dppf, PPh₃, P(t-Bu)₃, Pcy₃ or AsPh₃,particularly preferably dppf.

Starting with compounds of the formula (I-b)[X²=(4,4,5,5-tetramethyl-1,3,2-dioxoborolan)-2-yl], it is also possibleto prepare compounds of the formula (I) analogously to known methods (J.Org. Chem. 1995, 60, 7508; Tetrahedron Lett. 1997, 38, 3841).

Process C

Using tert-butyl(1R)-4-(2,6-difluorophenyl)-4-oxo-1-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]butylcarbamateand trifluoroacetic acid as starting materials, the course of theProcess C according to the invention can be illustrated by the equationbelow.

The formula (IV) provides a general definition of the aminoketonesrequired as starting materials for carrying out the Process C accordingto the invention. In this formula, R¹, R², R³, R⁴ and m each preferably,particularly preferably and very particularly preferably have thosemeanings which have already been mentioned in connection with thedescription of the compounds of the formula (I) according to theinvention as being preferred, particularly preferred etc. for theseradicals.

Optically active aminoketones of the formula (IV)

-   -   in which    -   R¹, R², R³, R⁴ and m are each as defined above, are novel. They        can be prepared by

-   α) reacting optically active N-Boc-lactams of the formula (V)

-   -   in which    -   R³, R⁴ and m are each as defined above,    -   with metallated aromatics of the formula (VI)

-   -   in which    -   R¹ and R² are each as defined above and    -   M¹ represents Li, MgCl, MgBr, MgI, ZnCl,    -   in the presence of a diluent at temperatures between −70° C. and        +70° C.

The formula (VI) provides a general definition of the metallatedaromatics required as starting materials for carrying out the Process α.In this formula, R¹ and R² preferably, particularly preferably and veryparticularly preferably have those meanings which have already beenmentioned in connection with the description of the compounds of theformula (I) according to the invention as being preferred, particularlypreferred etc. for these radicals. M¹ preferably represents Li, MgCl,MgBr, MgI, ZnCl, particularly preferably Li, MgCl, MgBr, MgI, veryparticularly preferably Li, MgCl, MgBr.

Some of the metallated aromatics of the formula (VI) are known, or theycan be prepared by known methods, such as, for example, lithiation orGrignard reaction, from the corresponding aromatics or halogenatedaromatics.

The formula (V) provides a general definition of the N-Boc-lactamsrequired as starting materials for carrying out the Process α. In thisformula, R³, R⁴ and m each preferably, particularly preferably and veryparticularly preferably have those meanings which have already beenmentioned in connection with the description of the compounds of theformula (I) according to the invention as being preferred, particularlypreferred etc. for these radicals.

N-Boc-lactams of the formula (V) are novel. They can be prepared, forexample, by

-   β) reacting optically active lactams of the formula (VII)

-   -   in which    -   R³, R⁴ and m are each as defined above,    -   by customary methods for example with di-tert-butyl dicarbonate        in the presence of a base (cf. Tetrahedron Lett. 1998, 39,        2705-2706).

The formula (VII) provides a general definition of the lactams requiredas starting materials for carrying out the Process β. In this formula,R³, R⁴ and m each preferably, particularly preferably and veryparticularly preferably have those meanings which have already beenmentioned in connection with the description of the compounds of theformula (I) according to the invention as being preferred, particularlypreferred etc. for these radicals.

Optically active lactams of the formula (VII) are novel. They can beprepared by

-   γ) chromatographing racemic lactams of the formula (VII-rac)

-   -   in which    -   R³, R⁴ and m are each as defined above,    -   on a chiral stationary silica gel phase and concentrating the        eluate under reduced pressure, or by

-   δ) reacting γ-ketocarboxylic acids of the formula (VIII)

-   -   in which    -   R³, R⁴ and m are each as defined above,    -   in a multi-step synthesis, or by

-   ε) reacting γ-ketocarboxylic acid esters of the formula (VIII-a)

-   -   in which    -   R represents alkyl and    -   R³, R⁴ and m are each as defined above,    -   in a multi-step synthesis.

The formula (VII-rac) provides a general definition of the racemiclactams required as starting materials for carrying out the Process γ.In this formula, R³, R⁴ and m each preferably, particularly preferablyand very particularly preferably have those meanings which have alreadybeen mentioned in connection with the compounds of the formula (I)according to the invention as being preferred, particularly preferredetc. for these radicals.

Racemic lactams of the formula (VII-rac) are known and can be preparedby known processes (WO 99/59968, WO 99/59967 and WO 98/22438).

When carrying out the Process γ, methods of preparative chromatography,preferably the High Performance Liquid Chromatography (HPLC) method, areemployed. Here, a chiral stationary silica gel phase is used. A silicagel derivative (for example mercaptopropyl silica gel) modified withN-methacryloyl-L-leucin-D-menthylamide has been found to be particularlysuitable for separating the compounds of the formula (VII-rac) (cf. EP-A0 379 917).

Surprisingly, the racemic lactams of the formula (VII-rac) can beseparated on a kg scale in a short period of time (gradients shorterthan 20 min) by repeated chromatography on relatively short columns [450mm×75 mm, (I.D.)], this process thus also being suitable for industrialuse. Compared to commercial stationary chiral phases, the material usedhas considerably higher enantioselectivity values α (α=16 as compared toα=3 to 4; the higher the α value, the better the separation of theenantiomers).

The multi-step Process δ according to the invention can be illustratedby the equation below.

γ-Ketocarboxylic acids of the formula (VIII) are condensed with2(S)-2-amino-2-phenylethanol to give bicyclic lactams of the formula(IX) which are predominantly obtained as one diastereomer.

Reductive cleavage of bicyclic lactams of the formula (IX) using a Lewisacid (for example TiCl₄) and a reducing agent (for example Et₃SiH) givesN-protected γ-lactams of the formula (X) (cf. J. Org. Chem. 1992, 57,1656).

The hydroxyl group in γ-lactams of the formula (X) can be converted intoa leaving group (in particular a chlorine atom, cf. TetrahedronAsymmetry 1996, 7, 1835) using a chlorinating agent (for example thionylchloride), giving chlorides of the formula (XI).

Dehydrohalogenation of (XI) by treatment with a base (for example KOtBu)gives N-vinyllactams of the formula (XII).

It is also possible to convert γ-lactams of the formula (X) directly,for example by treatment with a base (for example LiOH) in a suitablesolvent (for example DMSO) at temperatures between 60° C. and 140° C.into the N-vinyllactams of the formula (XII) (cf. J. Org. Chem. 1996,61, 5813).

Acid-promoted hydrolysis of (XII) (using, for example, 1 M HCl) givesγ-lactams of the formula (VII) (cf. J. Org. Chem. 1996, 61, 5813).

The formula (VIII) and the formulae (IX), (X), (XI) and (XII) providegeneral definitions of the γ-ketocarboxylic acids required as startingmaterials for carrying out the Process δ according to the invention andthe intermediates, respectively. In these formulae, R³, R⁴ and m eachpreferably, particularly preferably and very particularly preferablyhave those meanings which have already been mentioned in connection withthe description of the compounds of the formula (I) according to theinvention as being preferred, particularly preferred etc. for theseradicals.

Some of the γ-ketocarboxylic acids of the formula (VIII) are known. Someof the methods by which they can be prepared are known. γ-Ketocarboxylicacids of the formula (VIII) are obtained, for example, by reactingappropriate aromatics with succinic anhydride or succinic acid monoesterchloride in the presence of a Lewis acid (for example aluminiumchloride) and, if appropriate, in the presence of a diluent (for example1,2-dichlorethane) (cf., for example, Org. Prep. Proced. Int. 1995, 27,550-552).

In the case of aromatics which do not permit a Friedel-Crafts acylation,it is alternatively possible to use a corresponding organometallicderivative, such as, for example, a Grignard reagent (cf. Syn. Commun.1996, 26, 3897).

It is also possible to prepare γ-ketocarboxylic acids of the formula(VIII) by reducing α,β-unsaturated carbonyl compounds of the formula(XIII) using, for example, Zn dust in glacial acetic acid according tothe reaction scheme below (cf. Chem. Pharm. Bull. 1988, 36, 2050).

The formula (XIII) provides a general definition of the carbonylcompounds. In this formula, R³, R⁴ and m each preferably, particularlypreferably and very particularly preferably have those meanings whichhave already been mentioned in connection with the description of thecompounds of the formula (I) according to the invention as beingpreferred, particularly preferred etc. for these radicals.

Some of the α,β-unsaturated carbonyl compounds of the formula (XIII) areknown, and/or they can be prepared, for example, by condensingacetophenones of the formula (XIV) with glyoxalic acid in the presenceof a base (for example NaOH) and, if appropriate, in the presence of adiluent (for example water, EtOH) according to the reaction scheme below(cf., for example, J. Med. Chem. 1996, 39, 4396).

The formula (XIV) provides a general definition of the acetophenones. Inthis formula, R³, R⁴ and m each preferably, particularly preferably andvery particularly preferably have those meanings which have already beenmentioned in connection with the description of the compounds of theformula (I) according to the invention as being preferred, particularlypreferred etc. for these radicals. Acetophenones of the formula (XIV)are known.

The multi-step Process ε can be illustrated by the equation below.

The reaction of a γ-ketocarboxylic ester of the formula (VIII-a) withallylamine in the presence of ammonium chloride gives allylamides of theformula (XV) (cf. Houben-Weyl, Methoden der Organischen Chemie [Methodsof Organic Chemistry], 4th Edition, Volume VIII, Chapter 6, p. 653 ff.).

According to the Corey, Bakshi & Shibata protocol (CBS reduction), theketofunctionality in compounds of the formula (XV) can beenantioselectively reduced in the presence of a catalyst {for example(3aR)-1-methyl-3,3,6-triphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborol,commercially available} (cf. Angew. Chem. 1998, 110, 2093 and referencescited therein).

The subsequent cyclization of compounds of the formula (XVI) to giveN-allyllactams of the formula (XVII) can be carried out bydouble-deprotonation with KOtBu and reaction with tosyl chloride (cf.Synth. Commun. 1988, 18, 1159), without noticeable loss ofstereochemical information. In contrast to the literature reference, itis surprisingly possible to dispense with the use of the carcinogenichexamethylphosphoric triamide (HMPT) cosolvent.

The allyl protective group is removed in an aqueous THF solution in thepresence of toluenesulphonic acid with the addition of 10 mol % ofPd(Ph₃P)₄ (cf. Heterocycles 1997, 44, 213 and references cited therein),giving the lactam of the formula (VII). The desired enantiomer can beenriched by recrystallization from petroleum ether (40/60)/toluene.

The formula (VIII-a) and the formulae (XV), (XVI) and (XVII) providegeneral definitions of the γ-ketocarboxylic esters required as startingmaterials for carrying out the Process ε according to the invention andthe intermediates, respectively. In these formulae, R³, R⁴ and m eachpreferably, particularly preferably and very particularly preferablyhave those meanings which have already been mentioned in connection withthe description of the compounds of the formula (I) according to theinvention as being preferred, particularly preferred etc. for theseradicals.

γ-Ketocarboxylic esters of the formula (VIII-a) can be prepared from thecorresponding acids of the formula (VIII) by known esterificationprocesses.

Suitable acid binders for carrying out the Process B according to theinvention are in each case all of the inorganic and organic basescustomary for such reactions. Preference is given to using alkalineearth metal or alkali metal hydroxides, such as sodium hydroxide,calcium hydroxide, potassium hydroxide, or else ammonium hydroxide,alkali metal carbonates, such as sodium carbonate, potassium carbonate,potassium bicarbonate, sodium bicarbonate, alkali metal or alkalineearth metal acetates, such as sodium acetate, potassium acetate, calciumacetate, alkali metal fluorides, and also tertiary amines, such astrimethylamine, triethylamine, tributylamine, N,N-dimethylaniline,pyridine, N-methylpiperidine, N,N-dimethylaminopyridine,diazabicyclooctane (DABCO), diazabicyclononene (DBN) ordiazabicycloundecene (DBU). However, it is also possible to carry outthe process without additional acid binder or to use an excess of theamine component so that it simultaneously acts as acid binder.Particular preference is given to using barium hydroxide, tripotassiumphosphate, caesium carbonate, potassium carbonate, sodium carbonate,potassium acetate, triethylamine, KOtBu, caesium fluoride or potassiumfluoride.

Suitable diluents for carrying out the Processes B and C according tothe invention are in each case all customary inert organic solvents.Preference is given to using optionally halogenated aliphatic, alicyclicor aromatic hydrocarbons, such as petroleum ether, hexane, heptane,cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin;chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbontetrachloride, dichloroethane or trichloroethane; ethers, such asdiethyl ether, diisopropyl ether, methyl-t-butyl ether, methyl-t-amylether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethaheor anisole; nitriles, such as acetonitrile, propionitrile, n- ori-butyronitrile or benzonitrile; amides, such as N,N-dimethylformamide,N,N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone orhexamethylphosphoric triamide; esters, such as methyl acetate or ethylacetate, sulphoxides, such as dimethyl sulphoxide, or sulphones, such assulpholane.

Suitable eluents for carrying out the Process A according to theinvention are in each case all customary inert organic solvents and alsomixtures of these. Preference is given to using optionally halogenatedaliphatic, alicyclic or aromatic hydrocarbons, such as petroleum ether,hexane, heptane, cyclohexane; dichloromethane, chloroform; alcohols,such as methanol, ethanol, propanol; nitriles, such as acetonitrile;esters, such as methyl acetate or ethyl acetate. Particular preferenceis given to using aliphatic hydrocarbons, such as hexane or heptane, andalcohols, such as methanol or propanol, very particularly preferablyn-heptane and isopropanol or mixtures of these.

Suitable diluents for carrying out the Process B according to theinvention are, particularly preferably, acetone, dimethoxyethane,dioxane, THF, DMF, dimethylacetamide, DMSO, ethanol, toluene or, ifappropriate, mixtures of the diluents mentioned with water.

Suitable diluents for carrying out the Process C according to theinvention are, particularly preferably, methylene chloride, chloroform,toluene, methanol or ethanol.

Suitable acids for carrying out the Process C according to the inventionare in each case all customary Lewis acids or protic acids. Methods forremoving Boc are generally known (cf., for example, T. W. Greene, P. G.M. Wuts, Protective Groups in Organic Synthesis, Ed. 3, New York, Wiley& Sons, 1999, pp. 520-525). Preference is given to using trifluoroaceticacid, HCl or HBr for removing the Boc protective group.

When carrying out the Process A according to the invention, the reactiontemperatures can in each case be varied within a relatively wide range.In general, the process is carried out at temperatures between 10° C.and 60° C., preferably between 10° C. and 40° C., particularlypreferably at room temperature.

When carrying out the Process B according to the invention, the reactiontemperatures can in each case be varied within a relatively wide range.In general, the process is carried out at temperatures between 0° C. and140° C., preferably between 10° C. and 120° C., particularly preferablybetween 20° C. and 120° C.

When carrying out the Process C according to the invention, the reactiontemperatures can in each case be varied within a relatively wide range.In general, the process is carried out at temperatures between −20° C.and +120° C., preferably between −10° C., and 60° C.

When carrying out the Process A according to the invention, in generalan about 1% strength solution of the racemic compound (I-rac) is usedfor the chromatographic separation. However, it is also possible to useother concentrations. Work-up is carried out by customary methods. Ingeneral, the eluate is substantially concentrated and solid componentsare filtered off and, after washing with n-heptane, dried. The residueis, if appropriate, freed chromatographically of any impurities that maystill be present. For this purpose, the eluents used are mixtures ofn-hexane or cyclohexane and ethyl acetate, the composition of which hasto be adapted to the compound to be purified in each case.

When carrying out the Process B(i) according to the invention, ingeneral 1 mol or a slight excess of organometallic compound of theformula (II) is employed per mole of the compound of the formula (I-a).However, it is also possible to employ the reaction components in otherratios. Work-up is carried out by customary methods. In general, thereaction mixture is taken up in ethyl acetate and the organic phase iswashed with water, dried over sodium sulphate, filtered andconcentrated. If required, the residue is freed by customary methodssuch as chromatography or recrystallization from any impurities that maystill be present.

When carrying out the Process B(ii) according to the invention, ingeneral 1 mol or a slight excess of aromatic of the formula (III) isemployed per mole of the compound of the formula (I-b). However, it isalso possible to employ the reaction components in other ratios. Work-upis carried out by customary methods. In general, the reaction mixture istaken up in ethyl acetate and the organic phase is washed with water,dried over sodium sulphate, filtered and concentrated. If required, theresidue is freed by customary methods such as chromatography orrecrystallization from any impurities that may still be present.

When carrying out the Process B(iii) according to the invention, ingeneral 1 mol or a slight excess of a diboron compound and 1 mol or aslight excess of a (hetero)aromatic of the formula (III) and 3% of apalladium catalyst are employed per mole of the compound of the formula(I-a). However, it is also possible to employ the reaction components inother ratios. It is optionally possible initially to charge the compoundof the formula (I-a) or the compound of the formula (III). Work-up iscarried out by customary methods. In general, the reaction mixture isdiluted with water and extracted with ethyl acetate. The organic phaseis washed with water, dried over sodium sulphate, filtered andconcentrated. If required, the residue is freed by customary methodssuch as chromatography or recrystallization from any impurities that maystill be present.

When carrying out the Process C according to the invention, in general100 mol of a protic acid are employed per mole of the compound of theformula (IV). However, it is also possible to employ the reactioncomponents in other ratios. Work-up is carried out by customary methods.In general, the reaction mixture is concentrated, taken up in a suitablesolvent and adjusted to pH 12 using sodium hydroxide, and the organicphase is washed with water, dried over sodium sulphate, filtered andconcentrated. If required, the residue is freed by customary methodssuch as chromatography or recrystallization from any impurities that maystill be present.

The active compounds are suitable for controlling animal pests, inparticular insects, arachnids and nematodes, which are encountered inagriculture, in forestry, in the protection of stored products and ofmaterials, and in the hygiene sector, and have good plant tolerance andfavourable toxicity to warm-blooded animals. They may be preferablyemployed as plant protection agents. They are active against normallysensitive and resistant species and against all or some stages ofdevelopment. The abovementioned pests include:

From the order of the Isopoda, for example, Oniscus asellus,Armadillidium vulgare and Porcellio scaber.

From the order of the Diplopoda, for example, Blaniulus guttulatus.

From the order of the Chilopoda, for example, Geophilus carpophagus andScutigera spp.

From the order of the Symphyla, for example, Scutigerella immaculata.

From the order of the Thysanura, for example, Lepisma saccharina.

From the order of the Collembola, for example, Onychiurus armatus.

From the order of the Orthoptera, for example, Acheta domesticus,Gryllotalpa spp., Locusta migratoria migratorioides, Melanoplus spp. andSchistocerca gregaria.

From the order of the Blattaria, for example, Blatta orientalis,Periplaneta americana, Leucophaea maderae, Blattella germanica.

From the order of the Dermaptera, for example, Forficula auricularia.

From the order of the Isoptera, for example, Reticulitermes spp.

From the order of the Phthiraptera, for example, Pediculus humanuscorporis, Haematopinus spp., Linognathus spp., Trichodectes spp. andDamalinia spp.

From the order of the Thysanoptera, for example, Hercinothripsfemoralis, Thrips tabaci, Thrips palmi and Frankliniella accidentalis.

From the order of the Heteroptera, for example, Eurygaster spp.,Dysdercus intermedius, Piesma quadrata, Cimex lectularius, Rhodniusprolixus and Triatoma spp.

From the order of the Homoptera, for example, Aleurodes brassicae,Bemisia tabaci, Trialeurodes vaporariorum, Aphis gossypii, Brevicorynebrassicae, Cryptomyzus ribis, Aphis fabae, Aphis pomi, Eriosomalanigerum, Hyalopterus arundinis, Phylloxera Vastatrix , Pemphigus spp.,Macrosiphum avenae, Myzus spp., Phorodon humuli, Rhopalosiphum padi ,Empoasca spp., Euscelis bilobatus, Nephotettix cincticeps, Lecaniumcorni, Saissetia oleae, Laodelphax striatellus, Nilaparvata lugens,Aonidiella aurantii, Aspidiotus hederae, Pseudococcus spp. and Psyllaspp.

From the order of the Lepidoptera, for example, Pectinophoragossypiella, Bupalus piniarius, Cheimatobia brumata, Lithocolletisblancardella, Hyponomeuta padella, Plutella xylostella, Malacosomaneustria, Euproctis chrysorrhoea, Lymantria spp., Bucculatrixthurberiella, Phyllocnistis citrella, Agrotis spp., Euxoa spp., Feltiaspp., Earias insulana, Heliothis spp., Mamestra brassicae, Panolisflammea, Spodoptera spp., Trichoplusia ni, Carpocapsa pomonella, Pierisspp., Chilo spp., Pyrausta nubilalis, Ephestia kuehniella, Galleriamellonella, Tineola bisselliella, Tinea pellionella, Hofmannophilapseudospretella, Cacoecia podana, Capua reticulana, Choristoneurafumiferana, Clysia ambiguella, Homona magnanima, Tortrix viridana,Cnaphalocerus spp., Oulema oryzae.

From the order of the Coleoptera, for example, Anobium punctatum,Rhizopertha dominica, Bruchidius obtectus, Acanthoscelides obtectus,Hylotrupes bajulus, Agelastica alni, Leptinotarsa decemlineata, Phaedoncochleariae, Diabrotica spp., Psylliodes chrysocephala, Epilachnavarivestis, Atomaria spp., Oryzaephilus surinamensis, Anthonomus spp.,Sitophilus spp., Otiorrhynchus sulcatus, Cosmopolites sordidus,Ceuthorrhynchus assimilis, Hypera postica Dermestes spp., Trogoderma.spp., Anthrenus spp., Attagenus spp., Lyctus spp., Meligethes aeneus,Ptinus spp., Niptus hololeucus, Gibbium psylloides, Tribolium spp.,Tenebrio molitor, Agriotes spp., Conoderus spp., Melolontha melolontha,Amphimallon solstitialis, Costelytra zealandica and Lissorhoptrusoryzophilus.

From the order of the Hymenoptera, for example, Diprion spp., Hoplocampaspp.,Lasius spp., Monomorium pharaonis and Vespa spp.

From the order of the Diptera, for example, Aedes spp., Anopheles spp.,Culex spp., Drosophila melanogaster, Musca spp., Fannia spp., Calliphoraerythrocephala, Lucilia spp., Chrysomyia spp., Cuterebra spp.,Gastrophilus spp., Hyppobosca spp., Stomoxys spp., Oestrus spp.,Hypoderma spp., Tabanus spp., Tannia spp., Bibio hortulanus, Oscinellafrit, Phorbia spp., Pegomyia hyoscyami, Ceratitis capitata, Dacus oleae,Tipula paludosa, Hylemyia spp. and Liriomyza spp.

From the order of the Siphonaptera, for example, Xenopsylla cheopis andCeratophyllus spp.

From the class of the Arachnida, for example, Scorpio maurus,Latrodectus mactans, Acarus siro, Argas spp., Ornithodoros spp.,Dermanyssus gallinae, Eriophyes ribis, Phyllocoptruta oleivora,Boophilus spp., Rhipicephalus spp., Amblyomma spp., Hyalomma spp.,Ixodes spp., Psoroptes spp., Chorioptes spp., Sarcoptes spp., Tarsonemusspp., Bryobia praetiosa, Panonychus spp., Tetranychus spp.,Hemitarsonemus spp., Brevipalpus spp.

The phytoparasitic nematodes include, for example, Pratylenchus spp.,Radopholus similis, Ditylenchus dipsaci, Tylenchulus semipenetrans,Heterodera spp., Globodera spp., Meloidogyne spp., Aphelenchoides spp.,Longidorus spp., Xiphinema spp., Trichodorus spp., Bursaphelenchus spp.

In particular, the compounds of the formula (I) according to theinvention have excellent activity against caterpillars, beetle larvae,spider mites, aphids and leaf-mining flies.

If appropriate, the compounds according to the invention can, at certainconcentrations or application rates, also be used as herbicides ormicrobicides, for example as fungicides, antimycotics and bactericides.If appropriate, they can also be employed as intermediates or precursorsfor the synthesis of other active compounds.

All plants and plant parts can be treated in accordance with theinvention. Plants are to be understood as meaning in the present contextall plants and plant populations such as desired and undesired wildplants or crop plants (including naturally occurring crop plants). Cropplants can be plants which can be obtained by conventional plantbreeding and optimization methods or by biotechnological and recombinantmethods or by combinations of these methods, including the transgenicplants and including the plant cultivars protectable or not protectableby plant breeders' rights. Plant parts are to be understood as meaningall parts and organs of plants above and below the ground, such asshoot, leaf, flower and root, examples which may be mentioned beingleaves, needles, stalks, stems, flowers, fruit bodies, fruits, seeds,roots, tubers and rhizomes. The plant parts also include harvestedmaterial, and vegetative and generative propagation material, forexample cuttings, tubers, rhizomes, offsets and seeds.

Treatment according to the invention of the plants and plant parts withthe active compounds is carried out directly or by allowing thecompounds to act on the surroundings, environment or storage space bythe customary treatment methods, for example by immersion, spraying,evaporation, fogging, scattering, painting on and, in the case ofpropagation material, in particular in the case of seeds, also byapplying one or more coats.

The active compounds can be converted into the customary formulations,such as solutions, emulsions, wettable powders, suspensions, powders,dusts, pastes, soluble powders, granules, suspension-emulsionconcentrates, natural and synthetic materials impregnated with activecompound and microencapsulations in polymeric substances.

These formulations are produced in a known manner, for example by mixingthe active compounds with extenders, that is, liquid solvents, and/orsolid carriers, optionally with the use of surfactants, that isemulsifiers and/or dispersants, and/or foam-formers.

If the extender used is water, it is also possible to employ for exampleorganic solvents as auxiliary solvents. Essentially, suitable liquidsolvents are: aromatics such as xylene, toluene or alkylnaphthalenes,chlorinated aromatics or chlorinated aliphatic hydrocarbons such aschlorobenzenes, chloroethylenes or methylene chloride, aliphatichydrocarbons such as cyclohexane or paraffins, for example petroleumfractions, mineral and vegetable oils, alcohols such as butanol orglycol and also their ethers and esters, ketones such as acetone, methylethyl ketone, methyl isobutyl ketone or cyclohexanone, strongly polarsolvents such as dimethylformamide and dimethyl sulphoxide, and alsowater.

As solid carriers there are suitable:

for example ammonium salts and ground natural minerals such as kaolins,clays, talc, chalk, quartz, attapulgite, montrnorillonite ordiatomaceous earth, and ground synthetic minerals, such as highlydisperse silica, alumina and silicates; as solid carriers for granulesthere are suitable: for example crushed and fractionated natural rockssuch as calcite, marble, pumice, sepiolite and dolomite, and alsosynthetic granules of inorganic and organic meals, and granules oforganic material such as sawdust, coconut shells, maize cobs and tobaccostalks;

as emulsifiers and/or foam-formers there are suitable: for examplenonionic and anionic emulsifiers, such as polyoxyethylene fatty acidesters, polyoxyethylene fatty alcohol ethers, for example alkylarylpolyglycol ethers, alkylsulphonates, alkyl sulphates, arylsulphonatesand also protein hydrolysates;

as dispersants there are suitable: for example lignosulphite wasteliquors and methylcellulose.

Tackifiers such as carboxymethylcellulose and natural and syntheticpolymers in the form of powders, granules or latices, such as gumarabic, polyvinyl alcohol and polyvinyl acetate, as well as naturalphospholipids such as cephalins and lecithins, and syntheticphospholipids, can be used in the formulations. Other additives can bemineral and vegetable oils.

It is possible to use colorants such as inorganic pigments, for exampleiron oxide, titanium oxide and Prussian Blue, and organic dyestuffs,such as alizarin dyestuffs, azo dyestuffs and metal phthalocyaninedyestuffs, and trace nutrients such as salts of iron, manganese, boron,copper, cobalt, molybdenum and zinc.

The formulations generally comprise between 0.1 and 95% by weight ofactive compound, preferably between 0.5 and 90%.

The active compounds according to the invention can be used as such orin their formulations, as a mixture with other, also known activecompounds, such as insecticides, attractants, sterilizing agents,bactericides, acaricides, nematicides, fungicides, growth-regulatingsubstances or herbicides, in order, in this way, for example, to broadenthe spectrum of activity or to prevent the development of resistance. Inmany cases, synergistic effects are obtained, i.e. the activity of themixture exceeds the activity of the individual components. Theinsecticides include, for example, phosphoric acid esters, carbamates,carboxylates, chlorinated hydrocarbons, phenylureas and substancesproduced by microorganisms, inter alia.

Suitable co-components are, for example, the following compounds:

Fungicides:

aldimorph, ampropylfos, ampropylfos-potassium, andoprim, anilazine,azaconazole, Azoxystrobin,

-   benalaxyl, benodanil, benomyl, benzamacril, benzamacryl-isobutyl,    bialaphos, binapacryl, biphenyl, bitertanol, blasticidin-S,    bromuconazole, bupirimate, buthiobate,-   calcium polysulphide, capsimycin, captafol, captan, carbendazirn,    carboxin, carvon, quinomethionate, chlobenthiazone, chlorfenazole,    chloroneb, chloropicrin, chlorothalonil, chlozolinate, clozylacon,    cufraneb, cymoxanil, cyproconazole, cyprodinil, cyprofuram,-   debacarb, dichlorophen, diclobutrazole, diclofluanid, diclomezine,    dicloran, diethofencarb, difenoconazole, dimethirimol, dimethomorph,    diniconazole, diniconazole-M, dinocap, diphenylamine, dipyrithione,    ditalimfos, dithianon, dodemorph, dodine, drazoxolon,-   edifenphos, epoxiconazole, etaconazole, ethirimol, etridiazole,-   famoxadon, fenapanil, fenarimol, fenbuconazole, fenfuram,    fenitropan, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate,    fentin hydroxide, ferbarn, ferimzone, fluazinam, flumetover,    fluoromide, fluquinconazole, flurprimidol, flusilazole,    flusulfamide, flutolanil, flutriafol, folpet, fosetyl-aluminium,    fosetyl-sodium, fthalide, fuberidazole, furalaxyl, furametpyr,    furcarbonil, furconazole, furconazole-cis, firmecyclox,-   guazatine,-   hexachlorobenzene, hexaconazole, hymexazole,-   imazalil, imibenconazole, iminoctadine, iminoctadine albesilate,    iminoctadine triacetate, iodocarb, ipconazole, iprobenfos (IBP),    iprodione, irumamycin, isoprothiolane, isovaledione,-   kasugamycin, kresoxim-methyl, copper preparations, such as: copper    hydroxide, copper naphthenate, copper oxychloride, copper sulphate,    copper oxide, oxine-copper and Bordeaux mixture,-   mancopper, mancozeb, maneb, meferimzone, mepanipyrim, mepronil,    metalaxyl, metconazole, methasulfocarb, methfuroxam, metiram,    metomeclam, metsulfovax, mildiomycin, myclobutanil, myclozolin,-   nickel dimethyldithiocarbamate, nitrothal-isopropyl, nuarimol,-   ofurace, oxadixyl, oxamocarb, oxolinic acid, oxycarboxim,    oxyfenthiin,-   paclobutrazole, pefurazoate, penconazole, pencycuron, phosdiphen,    picoxystrobin, pimaricin, piperalin, polyoxin, polyoxorim,    probenazole, prochloraz, procymidone, propamocarb,    propanosine-sodium, propiconazole, propineb, pyraclostrobin,    pyrazophos, pyrifenox, pyrimethanil, pyroquilon, pyroxyfur,-   quinconazole, quintozene (PCNB),-   sulphur and sulphur preparations,-   tebuconazole, tecloftalam, tecnazene, tetcyclasis, tetraconazole,    thiabendazole, thicyofen, thifluzamide, thiophanate-methyl, thiram,    tioxymid, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol,    triazbutil, triazoxide, trichlamide, tricyclazole, tridemorph,    trifloxystrobin, triflumizole, triforine, triticonazole,-   uniconazole,-   validamycin A, vinclozolin, viniconazole,-   zarilamide, zineb, ziram and also-   Dagger G, OK-8705, OK-8801,-   α-(1,1-dimethylethyl)-β-(2-phenoxyethyl)-1H-1,2,4-triazole-1-ethanol,-   α-(2,4-dichlorophenyl)-β-fluoro-β-propyl-1H-1,2,4-triazole-1-ethanol,-   α-(2,4-dichlorophenyl)-β-methoxy-α-methyl-1H-1,2,4-triazole-1-ethanol,-   α-(5-methyl-1,3-dioxan-5-yl)-β-[[4-(trifluoromethyl)-phenyl]-methylene]-1H-1,2,4-triazole-1-ethanol,-   (5RS,6RS)-6-hydroxy-2,2,7,7-tetramethyl-5-(1H-1,2,4-triazol-1-yl)-3-octanone,-   (E)-α-(methoxyimino)-N-methyl-2-phenoxy-phenylacetamide,    1-isopropyl{2-methyl-1-[[[1-(4-methylphenyl)-ethyl]-amino]-carbonyl]-propyl}-carbamate,-   1-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-yl)-ethanone-O-(phenylmethyl)-oxime,-   1-(2-methyl-1-naphthalenyl)-1H-pyrrole-2,5-dione,-   1-(3,5-dichlorophenyl)-3-(2-propenyl)-2,5-pyrrolidinedione,-   1-[(diiodomethyl)-sulphonyl]-4-methyl-benzene,-   1-[[2-(2,4-dichlorophenyl)-1,3-dioxolan-2-yl]-methyl]-1H-imidazole,-   1-[[2-(4-chlorophenyl)-3-phenyloxiranyl]-methyl]-1H-1,2,4-triazole,-   1-[1-[2-[(2,4-dichlorophenyl)-methoxy]-phenyl]-ethenyl]-1H-imidazole,-   1-methyl-5-nonyl-2-(phenylmethyl)-3-pyrrolidinole,-   2′,6′-dibromo-2-methyl-4′-trifluoromethoxy-4′-trifluoro-methyl-1,3-thiazole-5-carboxanilide,-   2,2-dichloro-N-[1-(4-chlorophenyl)-ethyl]-1-ethyl-3-methyl-yclopropanecarboxamide,-   2,6-dichloro-5-(methylthio)-4-pyrimidinyl-thiocyanate,-   2,6-dichloro-N-(4-trifluoromethylbenzyl)-benzamide,-   2,6-dichloro-N-[[4-(trifluoromethyl)-phenyl]-methyl]-benzamide,-   2-(2,3,3-triiodo-2-propenyl)-2H-tetrazole,-   2-[(1-methylethyl)-sulphonyl]-5-(trichloromethyl)-1,3,4-thiadiazole,-   2-[[6-deoxy-4-O-(4-O-methyl-β-D-glycopyranosyl)-α-D-glucopyranosyl]-amino]-4-methoxy-1H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile,-   2-aminobutane,-   2-bromo-2-(bromomethyl)-pentanedinitrile,-   2-chloro-N-(2,3-dihydro-1,1,3-trimethyl-1H-inden-4-yl)-3-pyridinecarboxamide,-   2-chloro-N-(2,6-dimethylphenyl)-N-(isothiocyanatomethyl)-acetamide,-   2-phenylphenol (OPP),-   3,4-dichloro-1-[4-(difluoromethoxy)-phenyl]-1H-pyrrole-2,5-dione,-   3,5-dichloro-N-[cyano[(1-methyl-2-propynyl)-oxy]-methyl]-benzamide,-   3-(1,1-dimethylpropyl-1-oxo-1H-indene-2-carbonitrile,-   3-[2-(4-chlorophenyl)-5-ethoxy-3-isoxazolidinyl]-pyridine,-   4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-sulphonamide,-   4-methyl-tetrazolo[1,5-a]quinazolin-5(4H)-one,-   8-(1,1-dimethylethyl)-N-ethyl-N-propyl-1,4-dioxaspiro[4.5]decane-2-methanamine,-   8-hydroxyquinoline sulphate,-   9H-xanthene-2-[(phenylamino)-carbonyl]-9-carboxylic hydrazide,-   bis-(1-methylethyl)-3-methyl-4-[(3-methylbenzoyl)-oxy]-2,5-thiophenedicarboxylate,-   cis-1-(4-chlorophenyl)-2-(1H-1,2,4-triazol-1-yl)-cycloheptanol,-   cis-4-[3-[4-(1,1-dimethylpropyl)-phenyl-2-methylpropyl]-2,6-dimethyl-morpholine    hydrochloride,-   ethyl[(4-chlorophenyl)-azo]-cyanoacetate,-   potassium bicarbonate,-   methanetetrathiol-sodium salt,-   methyl    1-(2,3-dihydro-2,2-dimethyl-1H-inden-1-yl)-1H-imidazole-5-carboxylate,-   methyl N-(2,6-dimethylphenyl)-N-(5-isoxazolylcarbonyl)-DL-alaninate,-   methyl N-(chloroacetyl)-N-(2,6-dimethylphenyl)-DL-alaninate,-   N-(2,3-dichloro-4-hydroxyphenyl)-1-methyl-cyclohexanecarboxamide,-   N-(2,6-dimethylphenyl)-2-methoxy-N-(tetrahydro-2-oxo-3-furanyl)-acetamide,-   N-(2,6-dimethylphenyl)-2-methoxy-N-(tetrahydro-2-oxo-3-thienyl)-acetamide,-   N-(2-chloro-4-nitrophenyl)-4-methyl-3-nitro-benzenesulphonamide,-   N-(4-cyclohexylphenyl)-1,4,5,6-tetrahydro-2-pyrimidinamine,-   N-(4-hexylphenyl)-1,4,5,6-tetrahydro-2-pyrimidinamine,-   N-(5-chloro-2-methylphenyl)-2-methoxy-N-(2-oxo-3-oxazolidinyl)-acetamide,-   N-(6-methoxy)-3-pyridinyl)-cyclopropanecarboxamide,-   N-[2,2,2-trichloro-1-[(chloroacetyl)-amino]-ethyl]-benzamide,-   N-[3-chloro-4,5-bis(2-propinyloxy)-phenyl]-N′-methoxy-methanimidamide,-   N-formyl-N-hydroxy-DL-alanine-sodium salt,-   O,O-diethyl[2-(dipropylamino)-2-oxoethyl]-ethylphosphoramidothioate,-   O-methyl S-phenyl phenylpropylphosphoramidothioate,-   S-methyl 1,2,3-benzothiadiazole-7-carbothioate,-   spiro[2H]-1-benzopyran-2,1′(3′H)-isobenzofuran]-3′-one,-   4-[3,4-dimethoxyphenyl)-3-(4-fluorophenyl)-acryloyl]-morpholine.    Bactericides:-   bronopol, dichlorophen, nitrapyrin, nickel dimethyldithiocarbamate,    kasugamycin, octhilinone, furancarboxylic acid, oxytetracyclin,    probenazole, streptomycin, tecloftalam, copper sulphate and other    copper preparations.    Insecticides/Acaricides/Nematicides:-   abamectin, acephate, acetarniprid, acrinathrin, alanycarb, aldicarb,    aldoxycarb, alpha-cypermethrin, alphamethrin, amitraz, avermectin,    AZ 60541, azadirachtin, azamethiphos, azinphos A, azinphos M,    azocyclotin,-   Bacillus popilliae, Bacillus sphaericus, Bacillus subtilis, Bacillus    thuringiensis, baculoviruses, Beauveria bassiana, Beauveria tenella,    bendiocarb, benfuracarb, bensultap, benzoximate, betacyfluthrin,    bifenazate, bifenthrin, bioethanomethrin, biopermethrin,    bistrifluron, BPMC, bromophos A, bufencarb, buprofezin, butathiofos,    butocarboxim, butylpyridaben,-   cadusafos, carbaryl, carbofuran, carbophenothion, carbosulfan,    cartap, chloethocarb, chlorethoxyfos, chlorfenapyr, chlorfenvinphos,    chlorfluazuron, chlormephos, chlorpyrifos, chlorpyrifos M,    chlovaporthrin, chromafenozide, cis-resmethrin, cispermethrin,    clocythrin, cloethocarb, clofentezine, clothianidine, cyanophos,    cycloprene, cycloprothrin, cyfluthrin, cyhalothrin, cyhexatin,    cypermethrin, cyromazine,-   deltamethrin, demeton M, demeton S, demeton-S-methyl, diafenthiuron,    diazinon, dichlorvos, dicofol, diflubenzuron, dimethoate,    dimethylvinphos, diofenolan, disulfoton, docusat-sodium, dofenapyn,-   eflusilanate, emamectin, empenthrin, endosulfan, Entomopfthora spp.,    esfenvalerate, ethiofencarb, ethion, ethoprophos, etofenprox,    etoxazole, etrimfos,-   fenamiphos, fenazaquin, fenbutatin oxide, fenitrothion,    fenothiocarb, fenoxacrim, fenoxycarb, fenpropathrin, fenpyrad,    fenpyrithrin, fenpyroximate, fenvalerate, fipronil, fluazinam,    fluazuron, flubrocythrinate, flucycloxuron, flucythrinate,    flufenoxuron, flumethrin, flutenzine, fluvalinate, fonophos,    fosmethilan, fosthiazate, fubfenprox, furathiocarb,-   granulosis viruses,-   halofenozide, HCH, heptenophos, hexaflumuron, hexythiazox,    hydroprene,-   imidacloprid, indoxacarb, isazofos, isofenphos, isoxathion,    ivermectin,-   nuclear polyhedrosis viruses,-   lambda-cyhalothrin, lufenuron,-   malathion, mecarbam, metaldehyde, methamidophos, Metharhizium    anisopliae, Metharhizium flavoviride, methidathion, methiocarb,    methoprene, methomyl, methoxyfenozide, metolcarb, metoxadiazone,    mevinphos, milbemectin, milbemycin, monocrotophos,-   naled, nitenpyram, nithiazine, novaluron,-   omethoate, oxamyl, oxydemethon M,-   Paecilomyces fumosoroseus, parathion A, parathion M, permethrin,    phenthoate, phorate, phosalone, phosmet, phosphamidon, phoxim,    pirimicarb, pirimiphos A, pirimiphos M, profenofos, promecarb,    propargite, propoxur, prothiofos, prothoate, pymetrozine,    pyraclofos, pyresmethrin, pyrethruin, pyridaben, pyridathion,    pyrimidifen, pyriproxyfen,-   quinalphos,-   ribavirin,-   salithion, sebufos, silafluofen, spinosad, spirodiclofen, sulfotep,    sulprofos,-   tau-fluvalinate, tebufenozide, tebufenpyrad, tebupirimiphos,    teflubenzuron, tefluthrin, temephos, temivinphos, terbufos,    tetrachlorvinphos, tetradifon, theta-cypermethrin, thiacloprid,    thiarnethoxam, thiapronil, thiatriphos, thiocyclam hydrogen oxalate,    thiodicarb, thiofanox, thuringiensin, tralocythrin, tralomethrin,    triarathene, triazamate, triazophos, triazuron, trichlophenidine,    trichlorfon, triflumuron, trimethacarb,-   vamidothion, vaniliprole, Verticillium lecanii,-   YI 5302,-   zeta-cypermethrin, zolaprofos,-   (1R-cis)-[5-(phenylmethyl)-3-furanyl]-methyl-3-[(dihydro-2-oxo-3(2H)-furanylidene)-methyl]-2,2-dimethylcyclopropanecarboxylate,-   (3-phenoxyphenyl)-methyl-2,2,3,3-tetramethylcyclopropanecarboxylate,-   1-[(2-chloro-5-thiazolyl)methyl]tetrahydro-3,5-dimethyl-N-nitro-1,3,5-triazine-2(1H)-imine,-   2-(2-chloro-6-fluorophenyl)-4-[4-(1,1-dimethylethyl)phenyl]-4,5-dihydro-oxazole,-   2-(acetyloxy)-3-dodecyl-1,4-naphthalenedione,-   2-chloro-N-[[[4-(1-phenylethoxy)-phenyl]-amino]-carbonyl]-benzamide,    2-chloro-N-[[[4-(2,2-dichloro-1,1-difluoroethoxy)-phenyl]-amino]-carbonyl]-benzamide,-   3-methylphenyl propylcarbamate.-   4-[4-(4-ethoxyphenyl)-4-methylpentyl]-1-fluoro-2-phenoxy-benzene,-   4-chloro-2-(1,1-dimethylethyl)-5-[[2-(2,6-dimethyl-4-phenoxyphenoxy)ethyl]thio]-3(2H)-pyridazinone,-   4-chloro-2-(2-chloro-2-methylpropyl)-5-[(6-iodo-3-pyridinyl)methoxy]-3(2H)-pyryridazinone,    4-chloro-5-[(6-chloro-3-pyridinyl)methoxy]-2-(3,4-dichlorophenyl)-3(2H)-pyridazinone,-   Bacillus thuringiensis strain EG-2348,-   [2-benzoyl-1-(1,1-dimethylethyl)-hydrazinobenzoic acid,-   2,2-dimethyl-3-(2,4-dichlorophenyl)-2-oxo-1-oxaspiro[4.5]dec-3-en-4-yl    butanoate,-   [3-[(6-chloro-3-pyridinyl)methyl]-2-thiazolidinylidene]-cyanamide,    dihydro-2-(nitromethylene)-2H-1,3-thiazine-3(4H)-carboxaldehyde,    ethyl[2-[[1,6-dihydro-6-oxo-1-(phenylmethyl)-4-pyridazinyl]oxy]ethyl]-carbamate,-   N-(3,4,4-trifluoro-1-oxo-3-butenyl)-glycine,-   N-(4-chlorophenyl)-3-[4-(difluoromethoxy)phenyl]-4,5-dihydro-4-phenyl-1H-pyrazole-1-carboxamide,-   N-[(2-chloro-5-thiazolyl)methyl]-N′-methyl-N″-nitro-guanidine,-   N-methyl-N′-(1-methyl-2-propenyl)-1,2-hydrazinedicarbothioamide,-   N-methyl-N′-2-propenyl-1,2-hydrazinedicarbothioamide,-   O,O-diethyl[2-(dipropylamino)-2-oxoethyl]-ethylphosphoramidothioate,-   N-cyanomethyl-4-trifluoromethyl-nicotinamide-   3,5-dichloro-1-(3,3-dichloro-2-propenyloxy)-4-[3-(5-trifluoromethylpyridin-2-yloxy)-propoxy]-benzene.-   It is also possible to admix other known active compounds, such as    herbicides, fertilizers and growth regulators.

When used as insecticides, the active compounds according to theinvention can furthermore be present in their commercially availableformulations and in the use forms, prepared from these formulations, asa mixture with synergistic agents. Synergistic agents are compoundswhich increase the action of the active compounds according to theinvention, without it being necessary for the synergistic agent added tobe active itself.

The active compound content of the use forms prepared from thecommercially available formulations can vary within wide limits. Theactive compound concentration of the use forms can be from 0.0000001 to95% by weight of active compound, preferably between 0.0001 and 1% byweight.

The compounds are employed in a customary manner appropriate for the useforms.

When used against hygiene pests and pests of stored products, the activecompound is distinguished by an excellent residual action on wood andclay as well as a good stability to alkali on limed substrates.

As already mentioned above, it is possible to treat all plants and theirparts according to the invention. In a preferred embodiment, wild plantspecies and plant cultivars, or those obtained by conventionalbiological breeding, such as crossing or protoplast fusion, and partsthereof, are treated. In a further preferred embodiment, transgeneticplants and plant cultivars obtained by genetic engineering, ifappropriate in combination with conventional methods (GeneticallyModified Organisms), and parts thereof are treated. The term “parts” or“parts of plants” or “plant parts” has been explained above.

Particularly preferably, plants of the plant cultivars which are in eachcase commercially available or in use are treated according to theinvention. Plant cultivars are to be understood as meaning plants havingcertain properties (“traits”) which have been obtained by conventionalbreeding, by mutagenesis or by genetic engineering. These can becultivars, bio- or genotypes.

Depending on the plant species or plant cultivars, their location andgrowth conditions (soils, climate, vegetation period, diet), thetreatment according to the invention may also result in superadditive(“synergistic”) effects. Thus, for example, reduced application ratesand/or a widening of the activity spectrum and/or an increase in theactivity of the substances and compositions to be used according to theinvention, better plant growth, increased tolerance to high or lowtemperatures, increased tolerance to drought or to water or soil saltcontent, increased flowering performance, easier harvesting, acceleratedmaturation, higher harvest yields, better quality and/or a highernutritional value of the harvested products, better storage stabilityand/or processability of the harvested products are possible whichexceed the effects which were actually to be expected.

The transgenic plants or plant cultivars (i.e. those obtained by geneticengineering) which are preferably to be treated according to theinvention include all plants which, in the genetic modification,received genetic material which imparted particularly advantageoususeful traits to these plants. Examples of such traits are better plantgrowth, increased tolerance to high or low temperatures, increasedtolerance to drought or to water or soil salt content, increasedflowering performance, easier harvesting, accelerated maturation, higherharvest yields, better quality and/or a higher nutritional value of theharvested products, better storage stability and/or processability ofthe harvested products. Further and particularly emphasized examples ofsuch properties are a better defence of the plants against animal andmicrobial pests, such as against insects, mites, phytopathogenic fungi,bacteria and/or viruses, and also increased tolerance of the plants tocertain herbicidally active compounds. Examples of transgenic plantswhich may be mentioned are the important crop plants, such as cereals(wheat, rice), maize, soya beans, potatoes, cotton, oilseed rape andalso fruit plants (with the fruits apples, pears, citrus fruits andgrapes), and particular emphasis is given to maize, soya beans,potatoes, cotton and oilseed rape. Traits that are emphasized are inparticular increased defence of the plants against insects by toxinsformed in the plants, in particular those formed in the plants by thegenetic material from Bacillus thuringiensis (for example by the genesCryIA(a), CryIA(b), CryIA(c), CryIIA, CryIIIA, CryIIIB2, Cry9c Cry2Ab,Cry3Bb and CryIF and also combinations thereof) (hereinbelow referred toas “Bt plants”). Traits that are also particularly emphasized are theincreased defence of the plants against fungi, bacteria and viruses bysystemic acquired resistance (SAR), systemin, phytoalexins, elicitorsand resistance genes and corresponding expressed proteins and toxins.Traits that are furthermore particularly emphasized are the increasedtolerance of the plants to certain herbicidally active compounds, forexample imidazolinones, sulphonylureas, glyphosates or phosphinotricin(for example the “PAT” gene). The genes which impart the desired traitsin question can also be present in combination with one another in thetransgenic plants. Examples of “Bt plants” which may be mentioned aremaize varieties, cotton varieties, soya bean varieties and potatovarieties which are sold under the trade names YIELD GARD® (for examplemaize, cotton, soya beans), KnockOut® (for example maize), StarLink®(for example maize), Bollgard® (cotton), Nucotn® (cotton) and NewLeaf®(potato). Examples of herbicide-tolerant plants which may be mentionedare maize varieties, cotton varieties and soya bean varieties which aresold under the trade names Roundup Ready® (tolerance to glyphosate, forexample maize, cotton, soya bean), Liberty Link® (tolerance tophosphinotricin, for example oilseed rape), IMI® (tolerance toimidazolinones) and STS® (tolerance to sulphonylurea, for examplemaize). Herbicide-resistant plants (plants bred in a conventional mannerfor herbicide tolerance) which may be mentioned include the varietiessold under the name Clearfield® (for example maize). Of course, thesestatements also apply to plant cultivars having these genetic traits orgenetic traits still to be developed, which plants will be developedand/or marketed in the future.

The plants listed can be treated according to the invention in aparticularly advantageous manner with the compounds of the formula (I)and/or the active compound mixtures according to the invention. Thepreferred ranges stated above for the active compounds and/or mixturesalso apply to the treatment of these plants. Particular emphasis isgiven to the treatment of plants with the compounds or mixturesspecifically mentioned in the present text.

The active compounds according to the invention act not only againstplant, hygiene and stored product pests, but also in the veterinarymedicine sector against animal parasites (ectoparasites), such as hardticks, soft ticks, mange mites, leaf mites, flies (biting and licking),parasitic fly larvae, lice, hair lice, feather lice and fleas. Theseparasites include:

From the order of the Anoplurida, for example, Haematopinus spp.,Linognathus spp., Pediculus spp., Phtirus spp. and Solenopotes spp.

From the order of the Mallophagida and the suborders Amblycerina andIschnocerina, for example, Trimenopon spp., Menopon spp., Trinoton spp.,Bovicola spp., Wemeckiella spp., Lepikentron spp., Damalina spp.,Trichodectes spp. and Felicola spp.

From the order of the Diptera and the suborders Nematocerina andBrachycerina, for example, Aedes spp., Anopheles spp., Culex spp.,Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomyia spp.,Culicoides spp., Chrysops spp., Hybomitra spp., Atylotus spp., Tabanusspp., Haematopota spp., Philipomyia spp., Braula spp., Musca spp.,Hydrotaea spp., Stomoxys spp., Haematobia spp., Morellia spp., Fanniaspp., Glossina spp., Calliphora spp., Lucilia spp., Chrysomyia spp.,Wohlfahrtia spp., Sarcophaga spp., Oestrus spp., Hypoderma spp.,Gasterophilus spp., Hippobosca spp., Lipoptena spp. and Melophagus spp.

From the order of the Siphonapterida, for example Pulex spp.,Ctenocephalides spp., Xenopsylla spp. and Ceratophyllus spp.

From the order of the Heteropterida, for example, Cimex spp., Triatomaspp., Rhodnius spp. and Panstrongylus spp.

From the order of the Blattarida, for example Blatta orientalis,Periplaneta americana, Blattella germanica and Supella spp.

From the subclass of the Acaria (Acarida) and the orders of the Meta-and Mesostigmata, for example, Argas spp., Ornithodorus spp., Otobiusspp., Ixodes spp., Amblyomma spp., Boophilus spp., Dermacentor spp.,Haemophysalis spp., Hyalomma spp., Rhipicephalus spp., Dermanyssus spp.,Raillietia spp., Pneumonyssus spp., Stemostoma spp. and Varroa spp.

From the order of the Actinedida (Prostigmata) und Acaridida(Astigmata), for example, Acarapis spp., Cheyletiella spp.,Omithocheyletia spp., Myobia spp., Psorergates spp., Demodex spp.,Trombicula spp., Listrophorus spp., Acarus spp., Tyrophagus spp.,Caloglyphus spp., Hypodectes spp., Pterolichus spp., Psoroptes spp.,Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp.,Knemidocoptes spp., Cytodites spp. and Laminosioptes spp.

They have, for example, excellent activity against the developmentstages of ticks such as, for example, Amblyomma hebraeum, and againstparasitic flies such as, for example, Lucilia cuprina.

The active compounds of the formula (I) according to the invention arealso suitable for controlling arthropods which infest agriculturalproductive livestock, such as, for example, cattle, sheep, goats,horses, pigs, donkeys, camels, buffalo, rabbits, chickens, turkeys,ducks, geese and bees, other pets, such as, for example, dogs, cats,caged birds and aquarium fish, and also so-called test animals, such as,for example, hamsters, guinea pigs, rats and mice. By controlling thesearthropods, cases of death and reduction in productivity (for meat,milk, wool, hides, eggs, honey etc.) should be diminished, so that moreeconomic and easier animal husbandry is possible by use of the activecompounds according to the invention.

The active compounds according to the invention are used in theveterinary sector in a known manner by enteral administration in theform of, for example, tablets, capsules, potions, drenches, granules,pastes, boluses, the feed-through process and suppositories, byparenteral administration, such as, for example, by injection(intramuscular, subcutaneous, intravenous, intraperitoneal and thelike), implants, by nasal administration, by dermal use in the form, forexample, of dipping or bathing, spraying, pouring on and spotting on,washing and powdering, and also with the aid of moulded articlescontaining the active compound, such as collars, ear marks, tail marks,limb bands, halters, marking devices and the like.

When used for cattle, poultry, pets and the like, the active compoundsof the formula (I) can be used as formulations (for example powders,emulsions, free-flowing compositions), which comprise the activecompounds in an amount of 1 to 80% by weight, directly or after 100 to10 000-fold dilution, or they can be used as a chemical bath.

It has furthermore been found that the compounds according to theinvention have a strong insecticidal action against insects whichdestroy industrial materials.

The following insects may be mentioned as examples and as preferred—butwithout a limitation:

Beetles, such as

Hylotrupes bajulus, Chlorophorus pilosis, Anobium punctatum, Xestobiumrufovillosum, Ptilinus pecticornis, Dendrobium pertinex, Emobius mollis,Priobium carpini, Lyctus brunneus, Lyctus africanus, Lyctus planicollis,Lyctus linearis, Lyctus pubescens, Trogoxylon aequale, Minthesrugicollis, Xyleborus spec., Tryptodendron spec., Apate monachus,Bostrychus capucins, Heterobostrychus brunneus, Sinoxylon spec.,Dinoderus minutus.

Hymenopterons, such as

Sirex juvencus, Urocerus gigas, Urocerus gigas taignus, Urocerus augur.

Termites, such as

Kalotermes flavicollis, Cryptotermes brevis, Heterotermes indicola,Reticulitermes flavipes, Reticulitermes santonensis, Reticulitermeslucifugus, Mastotermes darwiniensis, Zootermopsis nevadensis,Coptotermes formosanus.

Bristletails, such as Lepisma saccarina.

Industrial materials in the present connection are to be understood asmeaning non-living materials, such as, preferably, plastics, adhesives,sizes, papers and cards, leather, wood and processed wood products andcoating compositions.

Wood and processed wood products are materials to be protected,especially preferably, from insect infestation.

Wood and processed wood products which can be protected by the agentsaccording to the invention or mixtures comprising these are to beunderstood as meaning, for example:

-   building timber, wooden beams, railway sleepers, bridge components,    boat jetties, wooden vehicles, boxes, pallets, containers, telegraph    poles, wood panelling, wooden windows and doors, plywood, chipboard,    joinery or wooden products which are used quite generally in    house-building or in building joinery.

The active compounds according to the invention can be used as such, inthe form of concentrates or in generally customary formulations, such aspowders, granules, solutions, suspensions, emulsions or pastes.

The formulations mentioned can be prepared in a manner known per se, forexample by mixing the active compounds with at least one solvent ordiluent, emulsifier, dispersing agent and/or binder or fixing agent, awater repellent, if appropriate siccatives and UV stabilizers and ifappropriate dyestuffs and pigments, and also other processingauxiliaries.

The insecticidal compositions or concentrates used for the preservationof wood and wood-derived timber products comprise the active compoundaccording to the invention in a concentration of 0.0001 to 95% byweight, in particular 0.001 to 60% by weight.

The amount of the compositions or concentrates employed depends on thenature and occurrence of the insects and on the medium. The optimumamount employed can be determined for the use in each case by a seriesof tests. In general, however, it is sufficient to employ 0.0001 to 20%by weight, preferably 0.001 to 10% by weight, of the active compound,based on the material to be preserved.

Solvents and/or diluents which are used are an organic chemical solventor solvent mixture and/or an oily or oil-like organic chemical solventor solvent mixture of low volatility and/or a polar organic chemicalsolvent or solvent mixture and/or water, and if appropriate anemulsifier and/or wetting agent.

Organic chemical solvents which are preferably used are oily or oil-likesolvents having an evaporation number above 35 and a flashpoint above30° C., preferably above 45° C. Substances which are used as such oilyor oil-like water-insoluble solvents of low volatility are appropriatemineral oils or aromatic fractions thereof, or solvent mixturescontaining mineral oils, preferably white spirit, petroleum and/oralkylbenzene.

Mineral oils having a boiling range from 170 to 220° C., white spirithaving a boiling range from 170 to 220° C., spindle oil having a boilingrange from 250 to 350° C., petroleum and aromatics having a boilingrange from 160 to 280° C., terpentine oil and the like, areadvantageously employed.

In a preferred embodiment, liquid aliphatic hydrocarbons having aboiling range from 180 to 210° C. or high-boiling mixtures of aromaticand aliphatic hydrocarbons having a boiling range from 180 to 220° C.and/or spindle oil and/or monochloronaphthalene, preferablyα-monochloronaphthalene, are used.

The organic oily or oil-like solvents of low volatility which have anevaporation number above 35 and a flashpoint above 30° C., preferablyabove 45° C., can be replaced in part by organic chemical solvents ofhigh or medium volatility, provided that the solvent mixture likewisehas an evaporation number above 35 and a flashpoint above 30° C.,preferably above 45° C., and that the insecticide/fungicide mixture issoluble or emulsifiable in this solvent mixture.

According to a preferred embodiment, some of the organic chemicalsolvent or solvent mixture is replaced by an aliphatic polar organicchemical solvent or solvent mixture. Aliphatic organic chemical solventscontaining hydroxyl and/or ester and/or ether groups, such as, forexample, glycol ethers, esters or the like, are preferably used.

Organic chemical binders which are used in the context of the presentinvention are the synthetic resins and/or binding drying oils which areknown per se, are water-dilutable and/or are soluble or dispersible oremulsifiable in the organic chemical solvents employed, in particularbinders consisting of or comprising an acrylate resin, a vinyl resin,for example polyvinyl acetate, polyester resin, polycondensation orpolyaddition resin, polyurethane resin, alkyd resin or modified alkydresin, phenolic resin, hydrocarbon resin, such as indene-comarone resin,silicone resin, drying vegetable oils and/or drying oils and/orphysically drying binders based on a natural and/or synthetic resin.

The synthetic resin used as the binder can be employed in the form of anemulsion, dispersion or solution. Bitumen or bituminous substances canalso be used as binders in an amount of up to 10% by weight. Dyestuffs,pigments, water-repelling agents, odour correctants and inhibitors oranticorrosive agents and the like which are known per se canadditionally be employed.

It is preferred according to the invention for the composition orconcentrate to comprise, as the organic chemical binder, at least onealkyd resin or modified alkyd resin and/or a drying vegetable oil. Alkydresins having an oil content of more than 45% by weight, preferably 50to 68% by weight, are preferably used according to the invention.

All or some of the binder mentioned can be replaced by a fixing agent(mixture) or a plasticizer (mixture). These additives are intended toprevent evaporation of the active compounds and crystallization orprecipitation. They preferably replace 0.01 to 30% of the binder (basedon 100% of the binder employed).

The plasticizers originate from the chemical classes of phthalic acidesters, such as dibutyl, dioctyl or benzyl butyl phthalate, phosphoricacid esters, such as tributyl phosphate, adipic acid esters, such asdi-(2-ethylhexyl) adipate, stearates, such as butyl stearate or amylstearate, oleates, such as butyl oleate, glycerol ethers or highermolecular weight glycol ethers, glycerol esters and p-toluenesulphonicacid esters.

Fixing agents are based chemically on polyvinyl alkyl ethers, such as,for example, polyvinyl methyl ether or ketones, such as benzophenone orethylenebenzophenone.

Possible solvents or diluents are, in particular, also water, ifappropriate as a mixture with one or more of the abovementioned organicchemical solvents or diluents, emulsifiers and dispersing agents.

Particularly effective preservation of wood is achieved by impregnationprocesses on a large industrial scale, for example vacuum, double vacuumor pressure processes. The ready-to-use compositions can also compriseother insecticides, if appropriate, and also one or more fungicides, ifappropriate.

Possible additional mixing partners are, preferably, the insecticidesand fungicides mentioned in WO 94/29 268. The compounds mentioned inthis document are an explicit constituent of the present application.

Especially preferred mixing partners which may be mentioned areinsecticides, such as chlorpyriphos, phoxim, silafluofin, alphamethrin,cyoluthrin, cypermethrin, deltamethrin, permethrin, imidacloprid, NI-25,flufenoxuron, hexaflumuron, transfluthrin, thiacloprid, methoxyfenozideand triflumuron, and also fungicides, such as epoxyconazole,hexaconazole, azaconazole, propiconazole, tebuconazole, cyproconazole,metconazole, imazalil, dichlorfluanid, tolylfluanid,3-iodo-2-propinyl-butyl carbamate, N-octyl-isothiazolin-3-one and4,5-dichloro-N-octylisothiazolin-3-one.

The compounds according to the invention can at the same time beemployed for protecting objects which come into contact with saltwateror brackish water, such as hulls, screens, nets, buildings, moorings andsignalling systems, against fouling.

Fouling by sessile Oligochaeta, such as Serpulidae, and by shells andspecies from the Ledamorpha group (goose barnacles), such as variousLepas and Scalpellum species, or by species from the Balanomorpha group(acorn barnacles), such as Balanus or Pollicipes species, increases thefrictional drag of ships and, as a consequence, leads to a markedincrease in operation costs owing to higher energy consumption andadditionally frequent residence in the dry dock.

Apart from fouling by algae, for example Ectocarpus sp. and Ceramiumsp., fouling by sessile Entomostraka groups, which come under thegeneric term Cirripedia (cirriped crustaceans), is of particularimportance.

Surprisingly, it has now been found that the compounds according to theinvention, alone or in combination with other active compounds, have anoutstanding antifouling action.

Using the compounds according to the invention, alone or in combinationwith other active compounds, allows the use of heavy metals such as, forexample, in bis(trialkyltin) sulphides, tri-n-butyltin laurate,tri-n-butyltin chloride, copper(I) oxide, triethyltin chloride,tri-n-butyl(2-phenyl-4-chlorophenoxy)tin, tributyltin oxide, molybdenumdisulphide, antimony oxide, polymeric butyl titanate,phenyl-(bispyridine)-bismuth chloride, tri-n-butyltin fluoride,manganese ethylenebisthiocarbamate, zinc dimethyldithiocarbamate, zincethylenebisthiocarbamate, zinc salts and copper salts of 2-pyridinethiol1-oxide, bisdimethyldithiocarbamoylzinc ethylene-bisthiocarbamate, zincoxide, copper(I) ethylene-bisdithiocarbamate, copper thiocyanate, coppernaphthenate and tributyltin halides to be dispensed with, or theconcentration of these compounds substantially reduced.

If appropriate, the ready-to-use antifouling paints can additionallycomprise other active compounds, preferably algicides, fungicides,herbicides, molluscicides, or other antifouling active compounds.

Preferably suitable components in combinations with the antifoulingcompositions according to the invention are:

-   algicides such as-   2-tert-butylamino-4-cyclopropylamino-6-methylthio-1,3,5-triazine,    dichlorophen, diuron, endothal, fentin acetate, isoproturon,    methabenzthiazuron, oxyfluorfen, quinoclamine and terbutryn;-   fungicides such as-   benzo[b]thiophenecarboxylic acid cyclohexylamide S,S-dioxide,    dichlofluanid, fluorfolpet, 3-iodo-2-propinyl butylcarbamate,    tolylfluanid and azoles such as azaconazole, cyproconazole,    epoxyconazole, hexaconazole, metconazole, propiconazole and    tebuconazole;-   molluscicides such as-   fentin acetate, metaldehyde, methiocarb, niclosamid, thiodicarb and    trimethacarb;-   or conventional antifouling active compounds such as-   4,5-dichloro-2-octyl-4-isothiazolin-3-one, diiodomethylparatryl    sulphone, 2-(N,N-dimethylthiocarbamoylthio)-5-nitrothiazyl,    potassium, copper, sodium and zinc salts of 2-pyridinethiol 1-oxide,    pyridine-triphenylborane, tetrabutyldistannoxane,    2,3,5,6-tetrachloro-4-(methylsulphonyl)-pyridine,    2,4,5,6-tetrachloroisophthalonitrile, tetramethylthiuram disulphide    and 2,4,6-trichlorophenylmaleiimide.

The antifouling compositions used comprise the active compound accordingto the invention of the compositions according to the invention in aconcentration of 0.001 to 50% by weight, in particular 0.01 to 20% byweight.

Moreover, the antifouling compositions according to the inventioncomprise the customary components such as, for example, those describedin Ungerer, Chem. Ind. 1985, 37, 730-732 and Williams, AntifoulingMarine Coatings, Noyes, Park Ridge, 1973.

Besides the algicidal, fungicidal, molluscicidal active compounds andinsecticidal active compounds according to the invention, antifoulingpaints comprise, in particular, binders.

Examples of recognized binders are polyvinyl chloride in a solventsystem, chlorinated rubber in a solvent system, acrylic resins in asolvent system, in particular in an aqueous system, vinyl chloride/vinylacetate copolymer systems in the form of aqueous dispersions or in theform of organic solvent systems, butadiene/styrene/acrylonitrilerubbers, drying oils such as linseed oil, resin esters or modifiedhardened resins in combination with tar or bitumens, asphalt and epoxycompounds, small amounts of chlorine rubber, chlorinated polypropyleneand vinyl resins.

If appropriate, paints also comprise inorganic pigments, organicpigments or colorants which are preferably insoluble in salt water.Paints may furthermore comprise materials such as colophonium to allowcontrolled release of the active compounds. Furthermore, the paints maycomprise plasticizers, modifiers which affect the rheological propertiesand other conventional constituents. The compounds according to theinvention or the abovementioned mixtures may also be incorporated intoself-polishing antifouling systems.

The active compounds according to the invention are also suitable forcontrolling animal pests, in particular insects, arachnids and mites,which are found in enclosed spaces such as, for example, dwellings,factory halls, offices, vehicle cabins and the like. They can beemployed alone or in combination with other active compounds andauxiliaries in domestic insecticide products for controlling thesepests. They are active against sensitive and resistant species andagainst all developmental stages. These pests include:

-   From the order of the Scorpionidea, for example, Buthus occitanus.-   From the order of the Acarina, for example, Argas persicus, Argas    reflexus , Bryobia spp., Dermanyssus gallinae, Glyciphagus    domesticus, Omithodorus moubat, Rhipicephalus sanguineus, Trombicula    alfreddugesi, Neutrombicula autumnalis, Dermatophagoides    pteronissimus, Dermatophagoides forinae.-   From the order of the Araneae, for example, Aviculariidae,    Araneidae.-   From the order of the Opiliones, for example, Pseudoscorpiones    chelifer, Pseudoscorpiones cheiridium, Opiliones phalangium.-   From the order of the Isopoda, for example, Oniscus asellus,    Porcellio scaber.-   From the order of the Diplopoda, for example, Blaniulus guttulatus,    Polydesmus spp.-   From the order of the Chilopoda, for example, Geophilus spp.-   From the order of the Zygentoma, for example, Ctenolepisma spp.,    Lepisma saccharina, Lepismodes inquilinus.-   From the order of the Blattaria, for example, Blatta orientalies,    Blattella germanica, Blattella asahinai, Leucophaea maderae,    Panchlora spp., Parcoblatta spp., Periplaneta australasiae,    Periplaneta americana, Periplaneta brunnea, Periplaneta fuliginosa,    Supella longipalpa.-   From the order of the Saltatoria, for example, Acheta domesticus.-   From the order of the Dermaptera, for example, Forficula    auricularia.-   From the order of the Isoptera, for example, Kalotermes spp.,    Reticulitermes spp.-   From the order of the Psocoptera, for example, Lepinatus spp.,    Liposcelis spp.-   From the order of the Coleptera, for example, Anthrenus spp.,    Attagenus spp., Dermestes spp., Latheticus oryzae, Necrobia spp.,    Ptinus spp., Rhizopertha dominica, Sitophilus granarius, Sitophilus    oryzae, Sitophilus zeamais, Stegobium paniceum.-   From the order of the Diptera, for example, Aedes aegypti, Aedes    albopictus, Aedes taeniorhynchus, Anopheles spp., Calliphora    erythrocephala, Chrysozona pluvialis, Culex quinquefasciatus, Culex    pipiens, Culex tarsalis, Drosophila spp., Fannia canicularis, Musca    domestica, Phlebotomus spp., Sarcophaga carnaria, Simulium spp.,    Stomoxys calcitrans, Tipula paludosa.-   From the order of the Lepidoptera, for example, Achroia grisella,    Galleria mellonella, Plodia interpunctella, Tinea cloacella, Tinea    pellionella, Tineola bisselliella.-   From the order of the Siphonaptera, for example, Ctenocephalides    canis, Ctenocephalides felis, Pulex irritans, Tunga penetrans,    Xenopsylla cheopis.-   From the order of the Hymenoptera, for example, Camponotus    herculeanus, Lasius fuliginosus, Lasius niger, Lasius umbratus,    Monomorium pharaonis, Paravespula spp., Tetramorium caespitum.-   From the order of the Anoplura, for example, Pediculus humanus    capitis, Pediculus humanus corporis, Phthirus pubis.-   From the order of the Heteroptera, for example, Cimex hemipterus,    Cimex lectularius, Rhodinus prolixus, Triatoma infestans.

In the field of household insecticides, they are used alone or incombination with other suitable active compounds, such as phosphoricacid esters, carbamates, pyrethroids, growth regulators or activecompounds from other known classes of insecticides.

They are used as aerosols, pressure-free spray products, for examplepump and atomizer sprays, automatic fogging systems, foggers, foams,gels, evaporator products with evaporator tablets made of cellulose orpolymer, liquid evaporators, gel and membrane evaporators,propeller-driven evaporators, energy-free, or passive, evaporationsystems, moth papers, moth bags and moth gels, as granules or dusts, inbaits for spreading or in bait stations.

The preparation and use of the substances according to the invention areillustrated by the examples below.

PREPARATION EXAMPLES

Processs A

Racemate Resolution: Δ¹-Pyrrolines of the Formula (I)

(+/−)-5-(2,6-Difluorophenyl)-2-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]-3,4-dihydro-2H-pyrrole(I-3) (8 g) is dissolved in 1 l of n-heptane/isopropanol 9:1(v/v=volume/volume). The solution is then fractionally chromatographedon the silica gel phase Chiralcel OD® [manufacturer: Daicel (Japan),column dimensions: 500 mm×40 mm (I.D.), particle size: 20 μm, flow rate:40 ml/min] by High Performance Liquid Chromatography using the mobilephase n-heptane/isopropanol 9:1 (v/v). To resolve the total amount,every 30 min 5 ml (corresponding in each case to 40 mg of the racemate)are applied to the column. The compounds are detected using a UVdetector, at a wavelength of 254 nm. Following analysis for enantiomericpurity, the appropriate eluate fractions are pooled and substantiallyconcentrated under reduced pressure and the residues are filtered offand, after washing with n-heptane, dried. The resulting crude product ispurified on silica gel (mobile phase: n-hexane/ethyl acetate, 1:9→1:4,in each case v/v).

This gives 7 g of(2R)-5-(2,6-difluorophenyl)-2-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]-3,4-dihydro-2H-pyrrole(I-3).

The following optically active Δ¹-pyrrolines of the formula (I) areobtained by

Process A:

No. Structure Optical rotation [α]_(D) ee value I-1

+44.07(c = 0.91, CH₃CN);23° C. 99.4% I-2

+2.80(c = 1.0, MeOH);20° C. 99.7% I-3

+7.70(c = 1.5, CHCl₃);20° C. 99.5% I-4

+31.29(c = 0.62, MeOH);20° C. 99.5% I-5

+36.7(c = 1.0, MeOH);20° C. 99.0% I-6

+32.2(c = 1.1, MeOH);20° C. 99.6% I-7

+45.9(c = 0.30, CHCl₃);20° C. 99.4%Process B: Palladium-Catalysed Coupling Reactions

4-[(2R)-5-(2,6-Difluorophenyl)-3,4-dihydro-2H-pyrrole-2-yl]phenyltrifluoromethanesulphonate (I-a-1) (1.01 g, 2.5 mmol),bis(pinacolato)diboron (0.76 g, 3.0 mmol), KOAc (0.74 g, 7.5 mmol),PdCl₂[dppf] (60 mg, 0.075 mmol) and dimethoxyethane (15 ml) are stirredunder an atmosphere of argon at 80° C. for 3.5 h. The reaction mixtureis cooled to room temperature, diluted with water and extracted withethyl acetate. The organic phase is washed with brine, dried over sodiumsulphate, filtered and concentrated under reduced pressure. The residuethat remains is taken up in dichloromethane, 5 g of Florisil are addedand the solution is concentrated. The crude product is purifiedchromatographically on silica gel (mobile phase: cyclohexane/ethylacetate, 4:1 v/v).

This gives 0.55 g (57% of theory) of(2R)-5-(2,6-difluorophenyl)-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-3,4-dihydro-2H-pyrrole(I-b-1).

HPLC: log P (pH 7)=4.47 (purity 96.6%);

Optical rotation: [α]_(D)=+24.8 (c=0.9, MeOH); 20° C.

4-[(2R)-5-(2,6-Difluorophenyl)-3,4-dihydro-2H-pyrrol-2-yl]phenyltrifluoromethanesulphonate (I-a-1) (1.01 g, 2.5 mmol),bis(pinacolato)diboron (0.76 g, 3.0 mmol), KOAc (0.74 g, 7.5 mmol),PdCl₂[dppf] (60 mg, 0.075 mmol) and dimethoxyethane (15 ml) are stirredat 80° C. for 3 h. The reaction mixture is cooled to room temperature.4-Trifluoromethoxyphenylbromobenzene (III-1) (0.72 g, 3 mmol),PdCl₂[dppf] (60 mg, 0.075 mmol) and 2 M aqueous Na₂CO₃ solution (7.5 ml)are then added, and the mixture is stirred at 80° C. for 16 h. Thereaction mixture is cooled to room temperature, diluted with water andextracted with ethyl acetate. The organic phase is washed with water,dried over sodium sulphate and filtered. Florisil (4 g) is added and thesolution is concentrated under reduced pressure. The crude product ispurified chromatographically on silica gel (mobile phase: n-hexane/ethylacetate, 1:9→1:4, in each case v/v).

This gives 0.61 g (59% of theory) of(2R)-5-(2,6-difluorophenyl)-2-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]-3,4-dihydro-2H-pyrrole(I-3).

HPLC: log P (pH 2.3)=4.08 (purity 94.4%);

Optical rotation: [α]_(D)=+33.9 (c=0.9, MeOH); 20° C.

4-[(2R)-5-(2,6-Difluorophenyl)-3,4-dihydro-2H-pyrrol-2-yl]phenyltrifluoromethanesulphonate (I-a-1) (1.01 g, 2.5 mmol),bis(neopentylglycolato)diboron (0.68 g, 3.0 mmol), KOAc (0.74 g, 7.5mmol), PdCl₂[dppf] (60 mg, 0.075 mmol) and N,N-dimethylacetamide (15 ml)are stirred at 80° C. for 3 h. The reaction mixture is cooled to roomtemperature. 4-Bromophenyl trifluoromethyl sulphone (III-11) (0.72 g, 3mmol), PdCl₂[dppf] (60 mg, 0.075 mmol) and 2 M aqueous Na₂CO₃ solution(7.5 ml) are then added and the mixture is stirred at 80° C. for 16 h.The reaction mixture is cooled to room temperature, diluted with waterand extracted with ethyl acetate. The organic phase is washed withwater, dried over sodium sulphate and filtered. Florisil (4 g) is addedarid the solution is concentrated under reduced pressure. The crudeproduct is purified chromatographically on silica gel (mobile phase:n-hexane/ethyl acetate, 4:1, v/v).

This gives 0.60 g (52% of theory) of(2R)-5-(2,6-difluorophenyl)-2-{4′-[(trifluoromethyl)sulphonyl]-1,1′-biphenyl-4-yl}-3,4-dihydro-2H-pyrrole(I-11).

HPLC: log P (pH 2.3)=3.92 (purity 100%);

Optical rotation: [α]_(D)=+36.0 (c=0.35, methanol); 20° C.

4-[(2R)-5-(2,6-Difluorophenyl)-3,4-dihydro-2H-pyrrol-2-yl]phenyltrifluoromethanesulphonate (I-a-1) (9.00 g, 22.2 mmol),4-{[tert-butyl(dimethyl)silyl]oxy}phenylboronic acid (II-1) (8.40 g,33.3 mmol), K₂CO₃ (6.14 g, 44.4 mmol), Pd[PPh₃]₄ (1.28 g, 1.1 mmol),dimethoxyethane (150 ml), and distilled water (50 ml) are stirred at 80°C. overnight. The reaction mixture is cooled to room temperature andtaken up in ethyl acetate (300 ml). The organic phase is washed withwater, dried over sodium sulphate, filtered and concentrated underreduced pressure. The crude products are purified by silica gelchromatography (mobile phase: toluene/ethyl acetate, 4:1 v/v).

This gives 7.67 g (75% of theory) of(2R)-2-(4′-{[tert-butyl(dimethyl)silyl]oxy}-1,1′-biphenyl-4-yl)-5-(2,6-difluorophenyl)-3,4-dihydro-2H-pyrrole(1-8) of melting point 33° C.

HPLC: log P (pH 2.3)=6.20 (purity 93.68%).

This gives 1.80 g (23% of theory) of4′-[(2R)-5-(2,6-difluorophenyl)-3,4-dihydro-2H-pyrrol-2-yl]-1,1′-biphenyl-4′-ol(I-9) of melting point 217° C.

HPLC: log P (pH 2.3)=1.93 (purity 98.48%).

The following further optically active Δ¹-pyrrolines of the formula (I)are obtained by

Process B:

No. Structure Optical rotation [α]_(D) log p/m.p. I-10

m.p. 146–148° C. I-11

+36.0(c = 0.35, MeOH);20° C. log P 3.92 I-12

I-13

I-14

m.p. 148–150° C.Process C

Conversion of Laclams of the Formula (VII) Into N-Boc-Lactams of theFormula (V)

(5R)-5-[4′-(Trifluoromethoxy)-1,1′-biphenyl-4-yl]-2-pyrrolidinone(VII-1) (0.51 g, 77.9% pure, about 1.23 mmol) is initially charged indichloromethane (10 ml). t-Butoxycarbonyl anhydride (1.9 mmol, 0.56 g)and dimethylaminopyridine (0.02 g, 0.32 mmol) are added, and thereaction mixture is stirred at room-temperature overnight. The mixtureis diluted with dichloromethane (40 ml) and the organic phase is washedsuccessively with 1 M HCl, saturated: aqueous sodium bicarbonatesolution and brine, dried over magnesium sulphate, filtered andconcentrated under reduced pressure.

This gives 0.42 g (75% of theory) of tert-butyl(5R)-2-oxo-5-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]-1-pyrrolidinecarboxylate (V-1), which is reacted further as crude product withoutadditional purification.

HPLC: log P (pH 2.3)=4.32 (purity 93.1%).

(5R)-5-(4-Bromophenyl)-2-pyrrolidinone (VII-2) (1.38 g, 5.7 mmol) isinitially charged in dichloromethane (40 ml). tert-Butoxycarbonylanhydride (6.9 mmol, 1.50 g) and dimethylaminopyridine (0.14 g, 1.14mmol) are added, and the reaction mixture is stirred at room temperaturefor two days. The organic phase is washed successively with 1 M HCl,saturated aqueous sodium bicarbonate solution and brine, dried overmagnesium sulphate, filtered and concentrated under reduced pressure.The crude product is stirred with isopropanol and filtered off withsuction.

This gives 0.71 g (35% of theory) of tert-butyl(2R)-2-(4-bromophenyl)-5-oxo-1-pyrrolidinecarboxylate (V-2).

HPLC: log P (pH 2.3)=3.04 (purity 96.5%).

The following compounds are synthesized analogously:

log P No. Structure (pH 2.3) V-3

3.31 V-4

3.02

Conversion of N-Boc-Lactams of the Formula (V) in to N-Boc-Aminoketonesof the Formula (IV)

Under an atmosphere of argon, 1,3-difluorobenzene (0.29 g, 2.55 mmol)is, at −78° C., initially charged in THF (30 ml). n-BuLi (1.6 M inhexane, 2.55 mmol, 1.59 ml) and tetrarnethylethylenediamine (2.55 mmol,0.38 ml) are successively added dropwise to this solution. The mixtureis stirred at −78° C. for 20 min, and compound (V-1) (1.70 mmol, 0.72 g)in THF (2 ml) is then added at this temperature. The reaction mixture isallowed to warm to room temperature overnight and then poured into water(10 ml). The aqueous phase is extracted with ethyl acetate (100 ml) andthe organic phase is washed with brine, dried over magnesium sulphate,filtered and concentrated under reduced pressure.

This gives 0.52 g (30% of theory) of tert-butyl(1R)-4-(2,6-difluorophenyl)-4-oxo-1-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]butylcarbamate(IV-1), which is reacted further as crude product without additionalpurification.

HPLC: log P (pH 2.3)=5.18 (purity 52.9%).

Under an atmosphere of argon, 1,3-difluorobenzene (0.31 g, 2.7 mmol) is,at −78° C., initially charged in THF (20 ml). n-BuLi (1.6 M in hexane,2.7 mmol, 1.69 ml) is added dropwise to this solution. The mixture isstirred at −78° C. for 15 min, and compound V-2 (1.80 mmol, 0.60 g) inTHF (2 ml) is then added dropwise at this temperature. The reactionmixture is allowed to warm to room temperature overnight and then pouredinto water (10 ml). The aqueous phase is extracted with ethyl acetate(100 ml) and the organic phase is washed with brine, dried overmagnesium sulphate, filtered and concentrated under reduced pressure.

This gives 0.65 g (60% of theory) of tert-butyl(1R)-1-(4-bromophenyl)-4-(,6-difluorophenyl)-4-oxobutylcarbamate (IV-2),which is reacted further as crude product without additionalpurification.

HPLC: log P (pH 2.3)=4.22 (purity 75.3%).

The following compounds are synthesized analogously:

No. Structure log P (pH 2.3) IV-3

4.37 IV-4

4.10

Conversion of N-Boc-Aminoketones of the Formula (IV) in to Pyrrolines ofthe Formula (I)

At 0° C., compound (IV-1) (0.10 g, 0.19 mmol) is initially charged indichloromethane (5 ml). Trifluoroacetic acid (0.14 ml, 18.7 mmol) isadded dropwise and the reaction mixture is stirred at room temperaturefor 3 h and then concentrated to dryness. The residue is taken up indichloromethane and adjusted to pH 12 using 2 M NaOH. The organic phaseis washed with water, dried over magnesium sulphate, filtered andconcentrated under reduced pressure.

This gives 0.09 g (˜100% of theory) of(2R)-5-(2,6-difluorophenyl)-2-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]-3,4-dihydro-2H-pyrrole(I-3).

HPLC: log P (pH 2.3)=4.13 (purity 90.4%);

Optical rotation: [α]_(D)=+33.9 (c=0.9, MeOH); 20° C.;

Enantiomeric excess (ee value): 99.0%.

At 0° C., compound (IV-2) (0.65 g, 75.3% pure) is initially charged indichloromethane (20 ml). Trifluoroacetic acid (1.08 ml, 14.0 mmol) isadded dropwise, and the reaction mixture is stirred at room temperaturefor 3 h and then concentrated to dryness. The residue is taken up inethyl acetate and adjusted to pH 11 using 1 M NaOH. The organic phase iswashed with water, dried over magnesium sulphate, filtered andconcentrated under reduced pressure. The crude product is purified bysilica gel chromatography (mobile phase: cyclohexane/ethyl acetate, 8:1v/v).

This gives 0.19 g (53% of theory) of(2R)-2-(4-bromophenyl)-5-(2,6-difluorophenyl)-3,4-dihydro-2H-pyrrole(I-15).

HPLC: log P (pH 2.3)=2.74 (purity 96.69%);

Enantiomeric excess (ee value): 99.9%.

The following compounds are synthesized analogously:

No. Structure Optical rotation [α]_(D) log P (pH 2.3) I-16

+34.1(c = 0.92, CHCl₃);20° C. 3.55 I-17

+48.9(c = 0.94, MeOH);20° C. 2.85Process γPreparation of the Optically Active Lactams of the Formula (VII) byRacemate Resolution

The racemate is resolved at room temperature by liquid chromatography onthe chiral stationary polyamide silica gel phase using the eluent ethylacetate and photometric detection. The chiral phase used is based on themonomer N-methacryloyl-L-leucine-d-menthylamide which, afterfree-radical polymerization, is covalently attached to a modified silicagel. Phases of this type are described, for example, in EP-A 0 379 917.Under the conditions given above, the dextrirotatory enantiomer elutesfirst.

-   Stationary phase: 1000 g of silica gel CSP; 10 μm, as described    above-   Column: 450 mm×75 mm-   Eluent: Ethyl acetate-   Flow rate: 100 ml/min-   UV detection: 254 nm-   Sample application: 6 g of racemate (=150 ml of a solution of 40 g    of racemate in 1 l of ethyl acetate)

The chromatographic separation conditions are set such that elution ofthe second enantiomer is accelerated by a short gradient with 100%methanol, thus reducing the total elution time considerably.

Following analysis for enantiomeric purity, the appropriate eluatefractions are pooled and substantially concentrated under reducedpressure and the residues are filtered off and, after washing withn-heptane, dried.

The enantiomeric purities of the lactams of the formula (VII) aredetermined by HPLC as follows:

-   Column: CSP analogously to the preparative separation (10 μm;    250×4.6 mm)-   Eluent: Ethyl acetate/methanol 25:1 (v/v)-   Flow rate: 1 mil/min-   UV detection: 280 nm

The following lactams of the formula (Vet) are obtained by Process γ:

No. Structure Optical rotation ee value VII-1

+18.5(c = 1.5, CHCl₃);20° C. 99.9% VII-3

+23.2(c = 0.5, MeOH);20° C. 99.4% VII-4

+23.7(c = 0.7, MeOH);20° C. 98.0% VII-5

+22.8(c = 0.9, MeOH);20° C. 99.4% VII-6

+26.0(c = 0.5, MeOH);20° C. 99.0%Process δ: Asymmetric Synthesis of Lactams of the Formula (VII)

(3S,7aS)-3-Phenyl-7a-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]tetrahydroiyrrolo-[2,1-b][1,3]oxazol-5(6H)-one(IX-1)

Using a Dean-Stark separator,4-oxo-4-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]butyric acid (VIII-1)(1.00 g, 32.5 mmol), 2(S)-2-amino-2-phenylethanol (4.46 g, 32.5 mmol),4-toluenesulphonic acid (1.10 g, 5.8 mmol) and toluene (400 ml) areheated under reflux for 3.5 h. The reaction mixture is cooled, filteredand concentrated. The residue is saturated with diisopropyl ether andfiltered off with suction.

Yield: 5.56 g, 39% of theory;

HPLC: log P (pH 2.3)=4.55 (purity 92.8%);

Optical rotation: [α]_(D)=+75.8 (c=0.9, MeOH); 20° C.;

Melting point: 104° C.

(3S,7aS)-7a-(4-Bromophenyl)-3-phenyltetrahydropyrrolo[2,1-b][1,3]oxazol-5(6H)-one(IX-2)

Using a Dean-Stark separator, 3-(4-bromobenzoyl)-propionic acid (VIII-2)(18.75 g, 72.9 mmol), 2(S)-2-amino-2-phenylethanol (10.0 g, 72.9 mmol),4-toluenesulphonic acid (2.47 g, 13.0 mmol) and toluene (400 ml) areheated under reflux for 3.5 h. The reaction mixture is cooled, filteredand concentrated under reduced pressure. The crude product is purifiedby silica gel chromatography (mobile phase: cyclohexane/ethyl acetate,6:1 v/v).

Yield: 15.47 g, 55% of theory;

HPLC: log P (pH 2.3)=3.36 (purity 92.3%);

Optical rotation: [α]_(D)=+82.0 (c=1.0, MeOH); 20° C.;

Melting point: 111-113° C.

(5R)-1-[(1S)-2-Hydroxy-1-phenylethyl]-5-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]-2-pyrrolidinone(X-1)

Compound (IX-1) (3.81 g, 8.7 mmol) is initially charged indichloromethane (75 ml) and, at −78° C., triethylsilane (3.37 g, 29mmol) and TiCl₄ (1 M solution in CH₂Cl₂, 19.1 ml, 19 mmol) aresuccessively added dropwise. The mixture is stirred at −78° C. for 2 hand then at room temperature overnight. The reaction mixture is cooledto 0° C. and saturated aqueous ammonium chloride solution (100 ml) isadded dropwise. The organic phase is washed with water, dried oversodium sulphate, filtered and concentrated under reduced pressure. Thecrude product is reacted further without additional purification.

Yield: 3.63 g (95% of theory);

HPLC: log P (pH 2.3)=3.80 (purity 96.9%).

(5R)-5-(4-Bromophenyl)-1-[(1S)-2-hydroxy-1-phenylethyl]-2-pyrrolidinone(X-2)

Compound (IX-2) (3.12 g, 8.7 mmol) is initially charged indichloromethane (75 ml) and, at −78° C., triethylsilane (3.37 g, 29mmol) and TiCl₄ (1 M solution in CH₂Cl₂, 19.1 ml, 19 mmol) aresuccessively added dropwise. The mixture is stirred at −78° C. for 2 h,and then at room temperature overnight. The reaction mixture is cooledto 0° C. and saturated aqueous ammonium chloride solution (100 ml) isadded dropwise. The organic phase is washed with water, dried oversodium sulphate, filtered and concentrated under reduced pressure. Thecrude product is reacted further without additional purification.

Yield: 3.12 g (˜100% of theory);

HPLC: log P (pH 2.3)=2.58 (purity 100%);

Optical rotation: [α]_(D)=+40.0 (c=1.0, MeOH); 20° C.

(5R)-1-[(1S)-2-Chloro-1-phenylethyl]-5-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]-2-pyrrolidinone(XI-1)

Compound (X-1). (0.44 g, 1.0 mmol) is initially charged in THF (10 ml),and thionyl chloride (0.29 g, 2.42 mmol) is added dropwise. The reactionmixture is stirred for 1.5 h and concentrated. The crude product isreacted further without additional purification.

Yield: 0.38 g (83% of theory)

HPLC: log P (pH 2.3)=4.78 (purity 93.1%).

(5R)-5-(4-Bromophenyl)-1-[(1S)-2-chloro-1-phenylethyl]-2-pyrrolidinone(XI-2)

Compound (X-2) (2.00 g, 5.0 mmol) is initially charged in THF (10 ml),and thionyl chloride (1.19 g, 10.0 mmol) is added dropwise. The reactionmixture is stirred for 1.5 h and concentrated. The crude product isreacted further without additional purification.

Yield: 1.69 g (82% of theory)

HPLC: log P (pH 2.3)=3.61 (purity 91.8%)

Optical rotation: [α]_(D)=+42.0 (c=0.85, MeOH); 20° C.

(5R)-1-(1-Phenylvinyl)-5-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]-2-pyrrolidinone(XII-1)

Compound (XI-1) (0.50 g, 1.1 mmol) is initially charged in tBuOH (5 ml),and KOtBu (0.26 g, 2.4 mmol) is added. The reaction mixture is stirredat 60° C. overnight, cooled and concentrated. The residue is taken up inethyl acetate and washed successively with 1 M HCl and water. Theorganic phase is dried over magnesium sulphate, filtered andconcentrated. The crude product is reacted further without additionalpurification.

Yield: 0.34 g (74% of theory)

HPLC: log P (pH 2.3)=4.35 (purity 98.4%).

(5R)-5-(4-Bromophenyl)-1-(1-phenylvinyl)-2-piyrrolidinone (XII-2)

Compound (XI-2) (1.00 g, 2.6 mmol) is initially charged in tBuOH (10ml), and KOtBu (0.64 g, 5.7 mmol) is added. The reaction mixture isstirred at 60° C. overnight, cooled and concentrated. The residue istaken up in ethyl acetate and washed successively with 1 M HCl andwater. The organic phase is dried over magnesium sulphate, filtered andconcentrated. The crude product is reacted further without additionalpurification.

Yield: 0.67 g (34% of theory)

HPLC: log P (pH 2.3)=3.18 (purity 45.75%).

(5R)-5-[4′-(Trifluoromethoxy)-1,1′-biphenyl-4-yl]-2-pyrrolidinone(VII-1)

Compound (XII-1) (0.98 g, 2.3 mmol) is initially charged in THF (5 ml).1 M HCl (5 ml) is added, the reaction mixture is stirred at 60° C. for 1h and cooled to room temperature, and ethyl acetate (100 ml) is added.The organic phase is washed successively with saturated aqueous sodiumbicarbonate solution and brine, dried over magnesium sulphate, filteredand concentrated. The crude product is reacted further withoutadditional purification.

Yield: 0.51 g (74% of theory)

HPLC: log P (pH 2.3)=2.95 (purity 77.9%)

Enantiomeric excess (ee value): 97.1% (using Method 1 for lactams).

(5R)-5-(4-Bromophenyl)-2-pyrrolidinone (VII-2)

Compound (XII-2) (0.57 g, 1.7 mmol) is initially charged in THF (3 ml).1 M HCl (3 ml) is added, and the reaction mixture is stirred at 60° C.for 1 h, cooled to room temperature and concentrated. The residue istaken up in in dichloromethane (30 ml) and, at 0° C., adjusted to pH 11using 1 N NaOH. The organic phase is washed with water, dried overmagnesium sulphate, filtered and concentrated. The crude product isreacted further without additional purification.

Yield: 0.36 g (84% of theory)

HPLC: log P (pH 2.3)=3.54 (purity 95.3%)

Optical rotation: [α]_(D)=+33.6 (c=1.0, MeOH); 20° C.

Enantiomeric excess (ee value): 99.8% (using Method 1 for lactams).

Process ε: Asymmetric Synthesis of Lactams of the Formula (VII)

Methyl-4-oxo-4-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]butanoate(VIII-a-1)

Crude 4-oxo-4-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]butyric acid (25g, content: 65%, GC, silylated, 100% method) is dissolved in a mixtureof methanol (50 ml) and 2,2-dimethoxypropane (11.5 g, 110 mmol), treatedwith trimethylsilyl chloride (0.75 g, 7 mmol) and stirred at 50° C. for16 h. The reaction mixture is then concentrated and the residue isrecrystallized from toluene.

Yield: 18.2 g

HPLC: log P (pH 2.3)=4.01.

N-Allyl-4-oxo-4-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]butanamide(XV-1)

Methyl-4-oxo-4-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]butanoate(VIII-a-1) (18.2 g, 52 mmol) is treated with allylamine (41.6 g, 730mmol) and ammonium chloride (1.8 g, 33 mmol) and heated under reflux for6 h. For work-up, the mixture is poured into ice-cold aqueous HCl (2 M)and extracted with ethyl acetate. The combined organic phases are dried(Na₂SO₄) and concentrated. The crude product (17.7 g, content: 84.5%,HPLC, 100% method) is recrystallized from toluene.

Yield: 8.6 g

HPLC: log P (pH 2.3)=3.34, 3.42.

(4S)-N-Allyl-4-hydroxy-4-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]butanamide(XVI-1)

Under argon, the anhydrousN-allyl-4-oxo-4-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]butanamide(XV-1) (2.26 g, 6 mmol) is, in a Schlenk tube which had been dried byheating, dissolved in anhydrous THF (40 ml) and, at 0° C., treated witha solution of(3aR)-1-methyl-3,3,6-triphenyltetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaborole(600 μl, 1 M in toluene). At 0° C., a solution of the BH₃*SMe₂ complex(7.1 ml, 0.59 M) is added dropwise over a period of 30 min to thissolution. The mixture is stirred at 0° C. for 1 h. The ice-bath isremoved, and the mixture is then stirred at room temperature for another6 h. MeOH (10 ml) is added carefully and the mixture is thenconcentrated. For work-up, the residue is filtered through silica gel 60(mobile phase: CH₃OH/CH₂Cl₂, 10:1).

Yield: 1.24 g

HPLC: log P (pH 2.3)=2.99

Enantiomeric excess (ee value): 87% (GC method).

(5R)-1-Allyl-5-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]-2-pyrrolidinone(XVII-1)

Under argon, KOtBu (0.64 g, 5.7 mmol) is suspended, in a Schlenk tubewhich had been dried by heating, in THF (5 ml, anhydrous). At 0° C., asolution of(4S)-N-allyl-4-hydroxy-4-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]butanamide(XVI-1) (0.99 g, 2.6 mmol) in THF (8 ml, anhydrous) is added dropwise.The reaction mixture is stirred at 0° C. for 1 h and a solution of tosylchloride (0.52 g, 2.7 mmol) in THF (5 ml, anhydrous) is then addeddropwise over a period of 20 min. The mixture is stirred at 0° C. for 2h and at room temperature for 16 h. For work-up, the mixture is admixedwith water, adjusted to pH 5 using HCl and extracted with ethyl acetate.The combined organic phases are dried (Na₂SO₄) and concentrated. Theresidue (0.85 g, content: 81%, HPLC, 100% method) is further purified byflash chromatography (mobile phase: ethyl acetate/petroleum ether(40/60), 1:1).

Yield: 0.55 g

HPLC: log P (pH 2.3)=3.88

Enantiomeric excess (ee value): 85% (GC method).

(5R)-5-[4′-(Trifluoromethoxy)-1,1′-biphenyl-4-yl]-2-pyrrolidinone(VII-1)

Under argon,(5R)-1-allyl-5-[4′-(trifluoromethoxy)-1,1′-biphenyl-4-yl]-2-pyrrolidinone(XVII-1) (0.41 g, 1.14 mmol) is initially charged in a Schlenk tubetogether with Pd[PPh₃]₄ (131.7 mg, 0.114 mmol) and p-toluenesulphonicacid hydrate (0.52 g, 2.74 mmol), and THF (2 ml, degassed) and 1 ml ofH₂O are added. The yellow suspension is heated under reflux for 3 h. Forwork-up, the mixture, which was cooled to room temperature, is dilutedwith NaHCO₃ solution and admixed with ethyl acetate and filtered throughkieselguhr. The combined organic phases are dried (Na₂SO₄) andconcentrated under reduced pressure.

Yield: 0.5 g (89% of theory)

HPLC: log P (pH 2.3)=3.00

Enantiomeric excess (ee value): 85% (using Method 2 for lactams).

A sample of the lactam which had been purified by chromatography wasrecrystallized from petroleum ether (40/60)/toluene.

Melting point: 164° C.

HPLC: purity 99%

Enantiomeric excess (ee value): 99% (using Method 2 for lactams).

The log P values given in the tables and Preparation Examples above aredetermined in accordance with EEC Directive 79/831 Annex V.A8 by HPLC(High Performance Liquid Chromatography) using a reversed-phase column(C 18). Temperature: 43° C.

The determination was carried out in the acidic range at pH 2.3 usingthe mobile phases 0.1% aqueous phosphoric acid and acetonitrile; lineargradient from 10% acetonitrile to 90% acetonitrile.

Calibration was carried out using unbranched alkan-2-ones (having 3 to16 carbon atoms) with known log P values (determination of the log Pvalues by the retention times using linear interpolation between twosuccessive alkanols).

The lambda max values were determined in the maxima of thechromatographic signals using the UV spectra from 200 nm to 400 nm.

The enantiomeric purity of the pyrrolines of the formula (I) wasdetermined by analytical HPLC using the following conditions:

-   Stationary phase: Chiralcel OD® (Daicel, Japan); 5 μm-   Column: 250 mm×4.6 mm (I.D.)-   Eluent: n-heptane/2-propanol 10:1-   Flow rate: 1 ml/min-   UV detection: 254 nm

The enantiomeric purity of the lactams of the formula (VII) wasdetermined by analytical HPLC using the following conditions (Method 1):

-   Stationary phase: Silica gel-CSP; 10 μm-   Column: 250 mm×4.6 mm (I.D.)-   Eluent: Ethyl acetate/methanol 25:1 (v/v)-   Flow rate: 1 ml/min-   UV detection: 280 nm

The enantiomeric purity of the lactams of the formula (VII) wasdetermined by analytical HPLC using the following conditions (Method 2):

-   Stationary phase: Chiralcel OD-H® (Daicel, Japan); 5 μm-   Column: 250 mm×4.6 mm (I.D.)-   Eluent: n-heptane/2-propanol 19:1 (v/v)-   Flow rate: 0.5 ml/min-   UV detection: 220 nm

The enantiomeric purity of the butanamides of the formula (XVI) and thepyrrolidinones of the formula (XVII) was determined by analytical GCusing the following conditions:

-   Stationary phase: Hydrodex-β-6TBDM-   Column: 25 m×0.25 mm (I.D.)-   Carrier gas: Helium-   Pressure: 120 kPa-   Injector temperature: 220° C.-   Detector: FID-   Temperature prog.: 13 min 120° C., 1° C./min to 220° C.

USE EXAMPLES Example A

Heliothis Armigera Test

Solvent: 30 parts by weight of dimethylformamide Emulsifier:  1 part byweight of alkylaryl polyglycol ether

To prepare a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration.

Soya bean shoots (Glycine max) are treated by being dipped into thepreparation of active compound of the desired concentration and arepopulated with caterpillars of the cotton bollworm (Heliothis armigera)while the leaves are still moist.

After the desired period of time, the kill in % is determined. 100%means that all caterpillars have been killed; 0% means that none of thecaterpillars have been killed.

Active compounds, active compound concentrations and test results areshown in the table below.

TABLE A Plant-damaging insects Heliothis armigera test Concentration ofactive compound Kill rate Active compound in ppm in % after 6 d

according totheinvention 8 100

comparativesubstance 8 0

according totheinvention 1.6 100

comparativesubstance 1.6 0

Example B

Heliothis Virescens Test

Solvent: 30 parts by weight of dimethylformamide Emulsifier:  1 part byweight of alkylaryl polyglycol ether

To prepare a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration.

Soya bean shoots (Glycine max) are treated by being dipped into thepreparation of active compound of the desired concentration and arepopulated with Heliothis virescens caterpillars while the leaves arestill moist.

After the desired period of time, the kill in % is determined. 100%means that all caterpillars have been killed; 0% means that none of thecaterpillars have been killed.

Active compounds, active compound concentrations and test results areshown in the table below.

TABLE B Plant-damaging insects Heliothis virescens test Concentration ofactive compound Kill rate Active compound in ppm in % after 6 d

known 0.32 20

according tothe invention 0.32 90

comparativesubstance 8 0

according tothe invention 1.6 100

comparativesubstance 1.6 15

according tothe invention 8 100

comparativesubstance 8 0

according tothe invention 40 100

Example C

Plutella Test

Solvent: 30 parts by weight of dimethylformamide Emulsifier:  1 part byweight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration.

Cabbage leaves (Brassica oleracea) are treated by being dipped into thepreparation of active compound of the desired concentration and arepopulated with caterpillars of the diamond back moth (Plutellaxylostella) while the leaves are still moist.

After the desired period of time, the kill in % is determined. 100%means that all caterpillars have been killed; 0% means that none of thecaterpillars have been killed.

Active compounds, active compound concentrations and test results areshown in the table below.

TABLE C Plant-damaging insects Plutella test Concentration of activecompound Kill rate Active compound in ppm in % after 6 d

known 0.01 0

according tothe invention 0.01 100

comparativesubstance 1.6 0

known 0.0128 45

according to 0.0128 45

comparativesubstance 1.6 5

according tothe invention 0.32 100

comparativesubstance 0.32 0

according tothe invention 0.064 100

Example D

Spodoptera Exigua Test

Solvent: 30 parts by weight of dimethylformamide Emulsifier:  1 part byweight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration.

Cabbage leaves (Brassica oleracea) are treated by being dipped into thepreparation of active compound of the desired concentration and arepopulated with caterpillars of the army worm (Spodoptera exigua) whilethe leaves are still moist.

After the desired period of time, the kill in % is determined. 100%means that all caterpillars have been killed; 0% means that none of thecaterpillars have been killed.

Active compounds, active compound concentrations and test results areshown in the table below.

TABLE D Plant-damaging insects Spodoptera exigua test Concentration ofactive compound Kill rate Active compound in ppm in % after 6 d

known 0.04 55

according totheinvention 0.04 100

comparativesubstance 8 0

according totheinvention 1.6 100

comparativesubstance 1.6 0

according totheinvention 1.6 100

comparativesubstance 1.6 0

according totheinvention 8 100

Example E

Spodoptera Frugiperda Test

Solvent: 30 parts by weight of dimethylformamide Emulsifier:  1 part byweight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration.

Cabbage leaves (Brassica oleracea) are treated by being dipped into thepreparation of active compound of the desired concentration and arepopulated with caterpillars of the army worm (Spodoptera frugiperda)while the leaves are still moist.

After the desired period of time, the kill in % is determined. 100%means that all caterpillars have been killed; 0% means that none of thecaterpillars have been killed.

Active compounds, active compound concentrations and test results areshown in the table below.

TABLE E Plant-damaging insects Spodoptera frugiperda test Concentrationof active Kill rate compound in % Active compound in ppm after 6 d

0.02 25

0.02 100

8 0

0.0128 20

0.0128 65

1.6 10

1.6 100

1.6 0

1.6 100

Example F

Tetranyhcus Test (OP-resistant/Dip Treatment)

Solvent: 30 parts by weight of dimethylformamide Emulsifier:  1 part byweight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration.

Bean plants (Phaseolus vulgaris) which are heavily infested by allstages of the greenhouse rat spider mite (Tetranychus urticae) aredipped into the preparation of active compound of the desiredconcentration.

After the desired period of time, the efficacy in % is determined. 100%means that all spider mites have been killed; 0% means that none of thespider mites have been killed.

Active compounds, active compound concentrations and test results areshown in the table below.

TABLE F Plant-damaging mites Tetranychus test (OP-resistant/diptreatment) Concentration of active Kill rate compound in % Activecompound in ppm after 7 d

0.32 0

0.32 90

8 0

0.0128 95

0.0128 0

0.01 98

Example G

Diabrotica Balteata Test (Larvae in Soil)

Critical Concentration Test/Soil Insects—Treatment of Transgenic Plants

Solvent: 7 parts by weight of dimethylformamide Emulsifier: 1 part byweight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amount of solvent, thestated amount of emulsifier is added and the concentrate is diluted withwater to the desired concentration.

The preparation of active compound is poured on to the soil. Here, theconcentration of active compound in the preparation is virtuallyirrelevant, only the amount by weight of active compound per volume unitof soil, which is stated in ppm (mg/l), matters. The soil is filled into0.25 l pots and these are allowed to stand at 20° C.

Immediately after preparation, 5 pre-germinated maize corns of thecultivar YIELD GUARD (trade mark of Monsanto Comp., USA) are placed intoeach pot. After 2 days, the test insects in question are placed into thetreated soil. After a further 7 days, the efficacy of the activecompound is determined by counting the maize plants that have emerged (1plant=20% efficacy).

Example H

Heliothis Virescens Test (Treatment of Transgenic Plants)

Solvent: 7 parts by weight of dimethylformamide Emulsifier: 1 part byweight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amount of solvent and thestated amount of emulsifier, and the concentrate is diluted with waterto the desired concentration.

Soya bean shoots (Glycine max) of the cultivar Roundup Ready (trade nameof Monsanto Comp. USA) are treated by being dipped into the preparationof active compound of the desired concentration and are populated withthe tobacco bud worm Heliothis virescens while the leaves are stillmoist.

After the desired period of time the kill in % is determined. 100% meansthat all caterpillars have been killed; 0% means that none of thecaterpillars have been killed.

Example I

Amblyomma Hebraeum (ER) (Polyphargous Tick Nymphs/Dip Treatment)

Test animals: Amblyomma hebraeum nymphs which have sucked themselvesfull Solvent: Dimethyl sulphoxide

20 mg of active compound are dissolved in 1 ml of dimethyl sulphoxide.To prepare a suitable formulation, the solution of active compound isdiluted with water to the concentration desired in each case.

10 nymphs which have sucked themselves full are immersed for 1 min inthe preparation of active compound to be tested. The animals aretransferred to petri dishes (∅ 9.5 cm) fitted with filter paper discsand covered. After the nymphs have remained in a controlled-environmentcabinet for 4 weeks, the ecdysis rate is determined.

100% means that none of the animals have undergone normal ecdysis. 0%means that all animals have undergone ecdysis.

Active compounds, active compound concentrations and test results areshown in the table below.

TABLE I Amblyomma hebraeum (EH) (polyphargous tick nymphs/dip treatment)Concentration of active compound Effects on Active compound in ppmecdysis in %

10 100

10 100

10 0

10 100

10 100

10 0

Example K

Amblyomma hebraeum (EH) (Polyphargous Tick Nymphs/Dip Treatment,Determination of the ED50)

Test animals: Amblyomma hebraeum nymphs which have sucked themselvesfull Solvent: Dimethyl sulphoxide

20 mg of active compound are dissolved in 1 ml of dimethyl sulphoxide.To prepare a suitable preparation, the solution of active compound isdiluted with water to the concentration desired in each case.

For the determination of the ED50 value, a dose-activity curve with theconcentration spectrum 1000, 300, 100, 30, 10, 3, 1, 0.3, 0.1, 0.03,0.01 ppm is prepared.

10 nymphs which have sucked themselves full are immersed for 1 min intothe preparation of active compound to be tested. The animals aretransferred to petri dishes (∅ 9.5 cm) fitted with filter paper discsand covered. After the nymphs have remained in a controlled-environmentcabinet for 4 weeks, the ecdysis rate is determined.

100% means that none of the animals have undergone normal ecdysis. 0%means that all animals have undergone ecdysis.

The data are calculated by a 4-parameter logistic curve fit using XLfit(ID Business Solutions Ltd.). If at 1000 ppm 50% mortality has not beenreached, the ED50 is judged to be not determinable.

Active compounds and test results are shown in the table below.

TABLE K Amblyomma hebraeum (EH) ED50 determination (polyphargous ticknymphs/dip treatment) Active compound ED 50 (ppm)

0.27

0.14

notdeterminable

0.58

0.20

549.86

1. An optically active Δ¹-pyrroline of the formula (I) having theformula


2. An optically active Δ¹-pyrroline of the formula (I) having theformula